A Computer Simulation of SARS-CoV-2 Mutation Spectra for Empirical Data Characterization and Analysis.

It is very important to compute the mutation spectra, and simulate the intra-host mutation processes by sequencing data, which is not only for the understanding of SARS-CoV-2 genetic mechanism, but also for epidemic prediction, vaccine, and drug design. However, the current intra-host mutation analysis algorithms are not only inaccurate, but also the simulation methods are unable to quickly and precisely predict new SARS-CoV-2 variants generated from the accumulation of mutations. Therefore, this study proposes a novel accurate strand-specific SARS-CoV-2 intra-host mutation spectra computation method, develops an efficient and fast SARS-CoV-2 intra-host mutation simulation method based on mutation spectra, and establishes an online analysis and visualization platform. Our main results include: (1) There is a significant variability in the SARS-CoV-2 intra-host mutation spectra across different lineages, with the major mutations from G- > A, G- > C, G- > U on the positive-sense strand and C- > U, C- > G, C- > A on the negative-sense strand; (2) our mutation simulation reveals the simulation sequence starts to deviate from the base content percentage of Alpha-CoV/Delta-CoV after approximately 620 mutation steps; (3) 2019-NCSS provides an easy-to-use and visualized online platform for SARS-Cov-2 online analysis and mutation simulation.

Assessing predictors of NEDA in RRMS patients initiating dimethyl fumarate in a real-world setting

IntroductionNo evidence of disease activity (NEDA) is a treatment goal when using disease modifying therapy for treating relapsing remitting multiple sclerosis (RRMS).1 However, predicting which patients may achieve NEDA is challenging.ObjectiveTo identify the baseline clinical and MRI features that predict NEDA in patients initiating dimethyl fumarate (DMF).Method: In our observational study, we retrospectively collected clinical and radiological data acquired for patients with RRMS initiating DMF. Demographics and clinical details at MS onset and at DMF initiation (baseline) were evaluated. We investigated the associations between all the baseline clinical and MRI findings and NEDA at 24 months using a combined multiple logistic regression.ResultsWe had a total of 670 patients in our cohort and only 339 (50%) achieved NEDA at 24 months. Lower EDSS (Log odds[95%CI]= -0.19[-0.30 to -0.03], p=0.01), lower number of new MRI lesions at baseline (Log odds[95%CI]= -0.14[-0.32 to -0.04], p=0.01) and lower number of relapses in the previous 12 months (Log odds[95%CI]= -0.39[-0.77 to -0.26], p=0.0001) significantly predicted NEDA at 24 months.ConclusionSignificant predictors for achieving NEDA were the number of relapses in the previous year, the number of new MRI lesions and the EDSS at DMF initiation. This could be useful in clinical practice to counsel patients regarding their potential response to DMF.

Management of the COVID-19 Pandemic in Singapore from 2020 to 2021: A Revisit

The first coronavirus disease 2019 (COVID-19) case was detected in Singapore on 23 January 2020. Over the two years, Singapore witnessed tightening and easing of policies in response to and in anticipation of new variants, stress on the healthcare sector, and new waves of infection. Upon confirming the reliability of the data using Benford's analysis, the collated COVID-19 data and trends were analyzed alongside the policies between 2020 and 2021 in Singapore. Due to the proactive nature of these policies, Singapore was largely successful in reducing the imported cases that would spill over and result in community waves of infection and death. The government has taken necessary steps to support the citizens and reduce the impact of the pandemic on the economy of the country. Furthermore, there were policies that were more responsive and there are lessons to be learned from neighboring countries on their management of the pandemic. Given the endemic approach the government has adopted, the efficacy of these policies comes down to its sustainability. Since the pandemic requires frequent revisiting of these policies, Singapore's long-term management of the pandemic (or endemic) and its impact comes down to the ability of the government to introduce sustainable policies and update these according to new developments in treatments, variants, and vaccines, bearing in mind the socioeconomic condition of the country.

Acute kidney injury and its association with mortality in Asian COVID-19 patients: A meta-analysis.

BACKGROUND: Previous evidence suggests that acute kidney injury (AKI) is common in patients with COVID-19 and associated with adverse outcomes. Moreover, the incidence and mortality of AKI in Asia are ambiguous. OBJECTIVE: Evaluating the risk factors and risk of death from AKI in -COVID-19 patients in Asia. MATERIALS AND METHODS: We conducted a meta-analysis of clinical observational studies of -COVID-19 patients in Asia. Outcome measures included: AKI in COVID-19 patients, overall mortality in COVID-19 patients, and mortality assessment in patients with AKI. The random-effects model was adopted, with heterogeneity and sensitivity analysis. RESULTS: 27 clinical studies (18,216 Asian patients with COVID-19) have been included in the study. The pooled incidence of AKI was 0.19 (95% CI 16 - 23%; I2 = 98.9%, p < 0.001); the pooled incidence of total mortality was 0.19 (95% CI 17 - 22%; I2 = 98.9%, p < 0.001). No publication bias was found (Egger's test, p = 0.396, 0.213). The pooled mortality in AKI patients with COVID-19 was 50% (95% CI 33 - 67%; I2 by random-effects model = 98.4%, p < 0.001). AKI was found to be a risk factor for death in stepwise regression analysis; age, diabetes, and hypertension were influencing factors for AKI risk in -COVID-19 patients. CONCLUSION: AKI is a common complication in Asian COVID-19 patients, and it is associated with an increase in mortality of Asian COVID-19 patients. Any treatment that protects the kidney may be a practical intervention to reduce the mortality of COVID-19 patients in Asia.

Fear of COVID-19 Among College Students: A Systematic Review and Meta-Analysis.

Background: Mental health issue among college students is routinely a major public health concern, and coronavirus disease 2019 (COVID-19) pandemic may have exacerbated the students' mental health issues which include psychological distress, panic disorder, insomnia, and posttraumatic stress symptoms. However, few studies reached a consensus on the impact of COVID-19 fear on mental health among college students. Therefore, we aimed to conduct a systematic review and meta-analysis that quantitatively synthesized the fear among college students during the COVID-19 pandemic. Methods: PubMed, EMBASE, CINAHL, and PsycINFO electronic databases were systematically searched to identify cross-sectional study reporting the state of COVID-19 fear examined by the Fear of COVID-19 Scale (FCV-19S) published up until November 20, 2021. Methodological quality was complied with the evaluation criteria of the Agency for Healthcare Research and Quality. The random effects model was employed to estimate the pooled mean of FCV-19S score. Subgroup analysis and meta-regression analysis were also conducted. Publication bias was assessed by Begg's test and funnel plot. Results: A total of 16 studies with a sample size of 11,872 were included. A pooled mean of FCV-19S score was 17.60 [95% confidence interval (CI): 16.41-18.78]. The mean of COVID-19 fear in women (17.11, 95% CI: 16.59-17.64) was higher than that in men (15.21, 95% CI: 14.33-16.08). The highest and lowest pooled means of FCV-19S score were observed in the studies conducted in multiple countries that include Israel, Russian, and Belarus (21.55, 95% CI: 20.77-22.33) and in Europe (16.52, 95% CI: 15.26-17.77), respectively. No significant publication bias was detected by Begg's test. Conclusions: College students experienced a moderate level of fear caused by COVID-19 pandemic. It is necessary to design and implement prevention programs that target the mental health of college students. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021287017, identifier: CRD42021287017.

Study of Viral Photoinactivation by UV-C Light and Photosensitizer Using a Pseudotyped Model.

Different light-based strategies have been investigated to inactivate viruses. Herein, we developed an HIV-based pseudotyped model of SARS-CoV-2 (SC2) to study the mechanisms of virus inactivation by using two different strategies; photoinactivation (PI) by UV-C light and photodynamic inactivation (PDI) by Photodithazine photosensitizer (PDZ). We used two pseudoviral particles harboring the Luciferase-IRES-ZsGreen reporter gene with either a SC2 spike on the membrane or without a spike as a naked control pseudovirus. The mechanism of viral inactivation by UV-C and PDZ-based PDI were studied via biochemical characterizations and quantitative PCR on four levels; free-cell viral damage; viral cell entry; DNA integration; and expression of reporter genes. Both UV-C and PDZ treatments could destroy single stranded RNA (ssRNA) and the spike protein of the virus, with different ratios. However, the virus was still capable of binding and entering into the HEK 293T cells expressing angiotensin-converting enzyme 2 (ACE-2). A dose-dependent manner of UV-C irradiation mostly damages the ssRNA, while PDZ-based PDI mostly destroys the spike and viral membrane in concentration and dose-dependent manners. We observed that the cells infected by the virus and treated with either UV-C or PDZ-based PDI could not express the luciferase reporter gene, signifying the viral inactivation, despite the presence of RNA and DNA intact genes.

Chromosome-Scale Genome of Masked Palm Civet (Paguma larvata) Shows Genomic Signatures of Its Biological Characteristics and Evolution.

The masked palm civet (Paguma larvata) is a small carnivore with distinct biological characteristics, that likes an omnivorous diet and also serves as a vector of pathogens. Although this species is not an endangered animal, its population is reportedly declining. Since the severe acute respiratory syndrome (SARS) epidemic in 2003, the public has been particularly concerned about this species. Here, we present the first genome of the P. larvata, comprising 22 chromosomes assembled using single-tube long fragment read (stLFR) and Hi-C technologies. The genome length is 2.41 Gb with a scaffold N50 of 105.6 Mb. We identified the 107.13 Mb X chromosome and one 1.34 Mb Y-linked scaffold and validated them by resequencing 45 P. larvata individuals. We predicted 18,340 protein-coding genes, among which 18,333 genes were functionally annotated. Interestingly, several biological pathways related to immune defenses were found to be significantly expanded. Also, more than 40% of the enriched pathways on the positively selected genes (PSGs) were identified to be closely related to immunity and survival. These enriched gene families were inferred to be essential for the P. larvata for defense against the pathogens. However, we did not find a direct genomic basis for its adaptation to omnivorous diet despite multiple attempts of comparative genomic analysis. In addition, we evaluated the susceptibility of the P. larvata to the SARS-CoV-2 by screening the RNA expression of the ACE2 and TMPRSS2/TMPRSS4 genes in 16 organs. Finally, we explored the genome-wide heterozygosity and compared it with other animals to evaluate the population status of this species. Taken together, this chromosome-scale genome of the P. larvata provides a necessary resource and insights for understanding the genetic basis of its biological characteristics, evolution, and disease transmission control.

Analysis of Career-Advancement for Medical School Graduates During the COVID-19 Pandemic at a Chinese Teaching Hospital.

The COVID-19 pandemic has led to widespread social and economic disruptions in the balance of labor market. Our study aims to analyze the career-advancement of medical school graduates during the COVID-19 pandemic and the associated influencing factors. We collected and compared the career-advancement data of medical school graduates at a Chinese teaching hospital from 2016 to 2020. A self-designed 20-element medical graduates employment questionnaire and a Chinese adaptation of the General self-efficacy scale were distributed by the Questionnaire Star platform. Univariate analysis (Pearson's Chi-square-test and Fisher's exact-test) and subsequent binary logistic regression were used. Findings demonstrated that the career-advancement rate of medical graduate students in 2020 is 71.3%, which is significantly lower than that for the preceding 4 years from 2016 to 2019 (p < 0.001). Of the 251 employed medical school graduates, 159 (63.3%) have signed an employment agreement or contract, 83 (33.1%) are pursuing continued education domestically, and 9 (3.6%) have offers from foreign institutions. Univariate analysis revealed statistical differences of medical graduates' employment among various specialties, oral defense completion, job search start date, CV submission times, participation in a probationary period, and self-efficacy. Significant predictors for successful employment were early job search and self-efficacy by logistic regression model (χ2 = 12.719, p < 0.001). Most medical graduates assumed that the COVID-19 pandemic had a major (40.6%) or moderate (48%) impact on career-advancement. The COVID-19 pandemic has profoundly impacted the career-advancement of medical school graduates in 2020. We should make adaptive changes to improve the career-advancement of medical graduates.

Harnessing Twitter data to survey public attention and attitudes towards COVID-19 vaccines in the UK.

Attitudes to COVID-19 vaccination vary considerably within and between countries. Although the contribution of socio-demographic factors to these attitudes has been studied, the role of social media and how it interacts with news about vaccine development and efficacy is uncertain. We examined around 2 million tweets from 522,893 persons in the UK from November 2020 to January 2021 to evaluate links between Twitter content about vaccines and major scientific news announcements about vaccines. The proportion of tweets with negative vaccine content varied, with reductions of 20-24% on the same day as major news announcement. However, the proportion of negative tweets reverted back to an average of around 40% within a few days. Engagement rates were higher for negative tweets. Public health messaging could consider the dynamics of Twitter-related traffic and the potential contribution of more targeted social media campaigns to address vaccine hesitancy.

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.

2019nCoVAS: Developing the Web Service for Epidemic Transmission Prediction, Genome Analysis, and Psychological Stress Assessment for 2019-nCoV.

Since the COVID-19 epidemic is still expanding around the world and poses a serious threat to human life and health, it is necessary for us to carry out epidemic transmission prediction, whole genome sequence analysis, and public psychological stress assessment for 2019-nCoV. However, transmission prediction models are insufficiently accurate and genome sequence characteristics are not clear, and it is difficult to dynamically assess the public psychological stress state under the 2019-nCoV epidemic. Therefore, this study develops a 2019nCoVAS web service (http://www.combio-lezhang.online/2019ncov/home.html) that not only offers online epidemic transmission prediction and lineage-associated underrepresented permutation (LAUP) analysis services to investigate the spreading trends and genome sequence characteristics, but also provides psychological stress assessments based on such an emotional dictionary that we built for 2019-nCoV. Finally, we discuss the shortcomings and further study of the 2019nCoVAS web service.

Contribution of Temperature Increase to Restrain the Transmission of COVID-19.

The COVID-19 outbreak has already become a global pandemic and containing this rapid worldwide transmission is of great challenge. The impacts of temperature and humidity on the COVID-19 transmission rate are still under discussion. Here, we elucidated these relationships by utilizing two unique scenarios, repeated measurement and natural experiment, using the COVID-19 cases reported from January 23 - February 21, 2020, in China. The modeling results revealed that higher temperature was most strongly associated with decreased COVID-19 transmission at a lag time of 8 days. Relative humidity (RH) appeared to have only a slight effect. These findings were verified by assessing SARS-CoV-2 infectivity under the relevant conditions of temperature (4°C-37°C) and RH (> 40%). We concluded that temperature increase made an important, but not determined, contribution to restrain the COVID-19 outbreak in China. It suggests that the emphasis of other effective controlling polices should be strictly implemented to restrain COVID-19 transmission in cold seasons.

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To propose the architectural layout for the big general hospital in the face of public health emergencies, we analyzed the conditions, methods, problems and countermeasures for the reconstruction of the isolation ward from the existing medical building layout of a general hospital. The affected areas met the requirements of isolation ward in the reconstruction, and realized the corresponding partition and separation of people. But the cost of occupying the medical room should be concerned. General hospital should be alerted to potential risks of public health emergencies. The characteristics of different construction types, defects, and the function of the hospital should be considered in the construction, rebuilding, and expansion of the hospital, which shouldnot only meet the needs of the development of the hospital daily usage but also consider dealing with emergent public health events. We can adopt the reasonable layout, including setting up a firewall-like device between the channel and the floor, an ordinary ward at ordinary times, and an independent space for emergency by pulling down the gate. This strategy can not only avoid the problem of low utilization rate of the space occupied by the corresponding area in the ward for diseases spread by air and droplets, maximizing the efficiency of the medical site, but also avoid the problem of emergency response to the temporary reconstruction.

Modeling the Prevalence of Asymptomatic COVID-19 Infections in the Chinese Mainland.

Recently, considerable efforts have been focused on intensifying the screening process for asymptomatic COVID-19 cases in the Chinese Mainland, especially for up to 10 million citizens living in Wuhan City by nucleic acid testing. However, a high percentage of domestic asymptomatic cases did not develop into symptomatic ones, which is abnormal and has drawn considerable public attention. Here, we aimed to investigate the prevalence of COVID-19 infections in the Chinese Mainland from a statistical perspective, as it is of referential significance for other regions. By conservatively assuming a development time lag from pre-symptomatic (i.e., referring to the infected cases that were screened before the COVID-19 symptom onset) to symptomatic as an incubation time of 5.2 days, our results indicated that 92.5% of those tested in Wuhan City, China, and 95.1% of those tested in the Chinese Mainland should have COVID-19 syndrome onset, which was extremely higher than their corresponding practical percentages of 0.8% and 3.3%, respectively. We propose that a certain false positive rate may exist if large-scale nucleic acid screening tests for asymptomatic cases are conducted in common communities with a low incidence rate. Despite adopting relatively high-sensitivity, high-specificity detection kits, we estimated a very low prevalence of COVID-19 infections, ranging from 10-6 to 10-4 in both Wuhan City and the Chinese Mainland. Thus, the prevalence rate of asymptomatic infections in China had been at a very low level. Furthermore, given the lower prevalence of the infection, close examination of the data for false positive results is necessary to minimize social and economic impacts.

Expert consensus on prevention and control of COVID-19 in the neurological intensive care unit (first edition).

During the COVID-19 epidemic, the treatment of critically ill patients has been increasingly difficult and challenging. During the epidemic, some patients with neurological diseases also have COVID-19, which could be misdiagnosed and cause silent transmission and nosocomial infection. Such risk is high in a neurological intensive care unit (NCU). Therefore, prevention and control of epidemic in critically ill patients is of utmost importance. The principle of NCU care should include comprehensive screening and risk assessment, weighing risk against benefits and reducing the risk of COVID-19 transmission while treating patients as promptly as possible.