COVID-19 and sarcopenia-related traits: a bidirectional Mendelian randomization study.

Background: Emerging evidence suggested that coronavirus disease 2019 (COVID-19) patients were more prone to acute skeletal muscle loss and suffer sequelae, including weakness, arthromyalgia, depression and anxiety. Meanwhile, it was observed that sarcopenia (SP) was associated with susceptibility, hospitalization and severity of COVID-19. However, it is not known whether there is causal relationship between COVID-19 and SP-related traits. Mendelian randomization (MR) was a valid method for inferring causality. Methods: Data was extracted from the COVID-19 Host Genetic Initiative and the UK Biobank without sample overlapping. The MR analysis was performed with inverse variance weighted, weighted median, MR-Egger, RAPS and CAUSE, MR-APSS. Sensitivity analysis was conducted with MR-Egger intercept test, Cochran's Q test, MR-PRESSO to eliminate pleiotropy. Results: There was insufficient result in the MR-APSS method to support a direct causal relationship after the Bonferroni correction. Most other MR results were also nominally consistent with the MR-APSS result. Conclusions: Our study first explored the causal relationship between COVID-19 and SP-related traits, but the result indicated that they may indirectly interact with each other. We highlighted that older people had better absorb enough nutrition and strengthen exercise to directly cope with SP during the COVID-19 pandemic.

Metabolomic analysis of porcine intestinal epithelial cells during swine acute diarrhea syndrome coronavirus infection.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an enveloped, positive single-stranded RNA virus belonging to Coronaviridae family, Orthocoronavirinae subfamily, Alphacoronavirus genus. As one of the main causes of swine diarrhea, SADS-CoV has brought huge losses to the pig industry. Although we have a basic understanding of SADS-CoV, the research on the pathogenicity and interactions between host and virus are still limited, especially the metabolic changes induced by SADS-CoV infection. Here, we utilized a combination of untargeted metabolomics and lipomics to analyze the metabolic alteration in SADS-CoV infected cells. Significant changes were observed in 1257 of 2225 metabolites identified in untargeted metabolomics, while the number of lipomics was 435 out of 868. Metabolic pathway enrichment analysis showed that amino acid metabolism, tricarboxylic acid (TCA) cycle and ferroptosis were disrupted during viral infection, suggesting that these metabolic pathways may partake in pathological processes related to SADS-CoV pathogenesis. Collectively, our findings gain insights into the cellular metabolic disorder during SADS-CoV infection, offer a valuable resource for further exploration of the relationship between virus and host metabolic activities, and provide potential targets for the development of antiviral drugs.

P(VDF-TrFE)/BaTiO3 Nanofibrous Membrane with Enhanced Piezoelectricity for High PM0.3 Filtration and Reusable Face Masks.

In the background of air pollution and regular COVID-19 prevention, personal protective masks are necessary for our daily life. However, protective masks with high PM0.3 filtration usually have poor air permeability and are mostly disposable, leading to a heavy burden on the environment. In this work, a reusable membrane based on piezoelectric poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] nanofibers embedded with BaTiO3 nanoparticles (BTO NPs) was developed. The P(VDF-TrFE)/BTO composite nanofibers not only have enhanced piezoelectricity and surface polarity but also have reduced diameters that could be beneficial for electrostatic adhesion, pole-polar interactions, and mechanical sieving to increase the PM0.3 capture capacity. Moreover, the BTO NPs also improved the charge storage capacity of the composite membrane, which could further enhance the PM0.3 filtration efficiency after corona treatment. The piezoelectric mask based on P(VDF-TrFE)/BTO composite nanofibers has high filtration efficiencies of 96% for PM0.3 and 98% for bacteria, while the pressure drop was only 182 Pa, which is lower than the commercial N95 standard of 343.2 Pa. Furthermore, the piezoelectric mask has a long and stable filtration performance after 5 cycles of 75% alcohol disinfection, demonstrating that the P(VDF-TrFE)/BTO composite membrane has a potential application in personal protective masks with comfortable and reusable properties.

Covalently Targeted Highly Conserved Tyr318 to Improve the Drug Resistance Profiles of HIV-1 NNRTIs: A Proof-of-Concept Study.

This study presents proof of concept for designing a novel HIV-1 covalent inhibitor targeting the highly conserved Tyr318 in the HIV-1 non-nucleoside reverse transcriptase inhibitors binding pocket to improve the drug resistance profiles. The target inhibitor ZA-2 with a fluorosulfate warhead in the structure was found to be a potent inhibitor (EC50 = 11-246 nM) against HIV-1 IIIB and a panel of NNRTIs-resistant strains, being far superior to those of NVP and EFV. Moreover, ZA-2 was demonstrated with lower cytotoxicity (CC50 = 125 µM). In the reverse transcriptase inhibitory assay, ZA-2 exhibited an IC50 value of 0.057 µM with the ELISA method, and the MALDI-TOF MS data demonstrated the covalent binding mode of ZA-2 with the enzyme. Additionally, the molecular simulations have also demonstrated that compounds can form covalent binding to the Tyr318.

Swine acute diarrhea syndrome coronavirus induces autophagy to promote its replication via the Akt/mTOR pathway.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an enveloped, single-stranded, positive-sense RNA virus belonging to the Coronaviridae family. Increasingly studies have demonstrated that viruses could utilize autophagy to promote their own replication. However, the relationship between SADS-CoV and autophagy remains unknown. Here, we reported that SADS-CoV infection-induced autophagy and pharmacologically increased autophagy were conducive to viral proliferation. Conversely, suppression of autophagy by pharmacological inhibitors or knockdown of autophagy-related protein impeded viral replication. Furthermore, we demonstrated the underlying mechanism by which SADS-CoV triggered autophagy through the inactivation of the Akt/mTOR pathway. Importantly, we identified integrin α3 (ITGA3) as a potential antiviral target upstream of Akt/mTOR and autophagy pathways. Knockdown of ITGA3 enhanced autophagy and consequently increased the replication of SADS-CoV. Collectively, our studies revealed a novel mechanism that SADS-CoV-induced autophagy to facilitate its proliferation via Akt/mTOR pathway and found that ITGA3 was an effective antiviral factor for suppressing viral infection.

Characteristics of nosocomial infection and coping countermeasures during normalized prevention and control of COVID-19

OBJECTIVE: To investigate the epidemiological characteristics of infectious diseases, especially COVID-19 and explore the prevention and control strategies for nosocomial infection under normalization of COVID-19 epidemic. METHODS: The epidemiological characteristics of nosocomial infection were analyzed, and the strategies for control of nosocomial infection were put forward based on the experience of Guizhou Provincial People's Hospital on control of nosocomial infection. RESULTS: The establishment of scientific prevention and control system, pre-inspection triage, protection of key departments and health care workers, treatment of patient, environmental cleaning and disinfection, management of medical waste and enhancement of monitoring of nosocomial infection and training were the important constituent parts of the prevention and control of nosocomial infection. CONCLUSION: COVID-19 has a large scale of impact and is very harmful. under normalization of COVID-19 epidemic continue to analyze and summarize the practical expertence of nosocomial infection, It is an important measure to put forward the coping strategies for nosocomial infection so as to ensure the medical quality and safety as well as to prevent infectious disease epidemic from spreading through hospitals.

Clinical and epidemiological investigation of a child with asymptomatic COVID-19 infection following reoccurrence.

Objective: To investigate the case of a child infected with coronavirus disease 2019 (COVID-19) who had subsequent viral reactivation. Methods: We retrospectively analyzed the clinical manifestations, epidemiological data, laboratory and imaging examinations, treatment, and follow-up of the child. And then, we searched related literature using PubMed. Results: The 9-year-old boy was exposed to COVID-19 in Malawi and tested positive for NAT in Haikou, China. He was asymptomatic and admitted to our hospital. After six negative NATs, he was discharged from the hospital and quarantined in a hotel. His infection was reactivated again after 22 days (interval between first and last positive NATs). The cycle threshold (Ct) values of positive tests were 25 and 31, and the gene sequencing viral loads were very low. The viral strain Kenya/P2601/2020, a variant of the hCoV-19/Wuhan/IVDC-HB-01/2019 genome (GISAID accession IL: EPI_ISL_402119), was found when polymerase chain reaction enrichment was used to sequence the virus. However, people around him tested negative for COVID-19. Conclusion: First, we confirmed the reactivation of COVID-19 in a child. The risk of recurrent infection with SARS-CoV-2 was low, and the policy of strictly isolating patients carrying long-term viral ribonucleic acid should be reconsidered. The interval positivity was most likely due to incorrect sampling and/or testing methods. SGS and aB testing are recommended for children with viral reactivation. Second, SARS-CoV-2 viral reactivation cannot be ruled out. The possible mechanisms, such as prolonged infection and viral latent reactivation, need further investigation.

Case report: Application of nirmatrelvir/ritonavir to treat COVID-19 in a severe aplastic anemia child after allogeneic hematopoietic stem cell transplantation

We present a case report of successful treatment with nirmatrelvir/ritonavir (Paxlvoid) for a severe aplastic anemia child with COVID-19, cytopenia, and mixed chimerism of donor hematopoietic cells at 3 months after allogeneic hematopoietic stem cell transplantation. After the 5-day entire course of treatment, the clinical symptoms were relieved, cycle threshold values of ORF1a/b and N genes increased from 22.60 and 22.15 to 34.52 and 33.84, respectively, and the peripheral blood counts gradually recovered without graft failure. Nirmatrelvir/ritonavir can effectively inhibit the replication of SARS-CoV-2 without any significant adverse effects.

XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity.

XIAP-associated factor 1 (XAF1) is an interferon (IFN)-stimulated gene (ISG) that enhances IFN-induced apoptosis. However, it is unexplored whether XAF1 is essential for the host fighting against invaded viruses. Here, we find that XAF1 is significantly upregulated in the host cells infected with emerging RNA viruses, including influenza, Zika virus (ZIKV), and SARS-CoV-2. IFN regulatory factor 1 (IRF1), a key transcription factor in immune cells, determines the induction of XAF1 during antiviral immunity. Ectopic expression of XAF1 protects host cells against various RNA viruses independent of apoptosis. Knockout of XAF1 attenuates host antiviral innate immunity in vitro and in vivo, which leads to more severe lung injuries and higher mortality in the influenza infection mouse model. XAF1 stabilizes IRF1 protein by antagonizing the CHIP-mediated degradation of IRF1, thus inducing more antiviral IRF1 target genes, including DDX58, DDX60, MX1, and OAS2. Our study has described a protective role of XAF1 in the host antiviral innate immunity against RNA viruses. We have also elucidated the molecular mechanism that IRF1 and XAF1 form a positive feedback loop to induce rapid and robust antiviral immunity. IMPORTANCE Rapid and robust induction of antiviral genes is essential for the host to clear the invaded viruses. In addition to the IRF3/7-IFN-I-STAT1 signaling axis, the XAF1-IRF1 positive feedback loop synergistically or independently drives the transcription of antiviral genes. Moreover, XAF1 is a sensitive and reliable gene that positively correlates with the viral infection, suggesting that XAF1 is a potential diagnostic marker for viral infectious diseases. In addition to the antitumor role, our study has shown that XAF1 is essential for antiviral immunity. XAF1 is not only a proapoptotic ISG, but it also stabilizes the master transcription factor IRF1 to induce antiviral genes. IRF1 directly binds to the IRF-Es of its target gene promoters and drives their transcriptions, which suggests a unique role of the XAF1-IRF1 loop in antiviral innate immunity, particularly in the host defect of IFN-I signaling such as invertebrates.

Cold Atmospheric Plasma Ameliorates Skin Diseases Involving Reactive Oxygen/Nitrogen Species-Mediated Functions.

Skin diseases are mainly divided into infectious diseases, non-infectious inflammatory diseases, cancers, and wounds. The pathogenesis might include microbial infections, autoimmune responses, aberrant cellular proliferation or differentiation, and the overproduction of inflammatory factors. The traditional therapies for skin diseases, such as oral or topical drugs, have still been unsatisfactory, partly due to systematic side effects and reappearance. Cold atmospheric plasma (CAP), as an innovative and non-invasive therapeutic approach, has demonstrated its safe and effective functions in dermatology. With its generation of reactive oxygen species and reactive nitrogen species, CAP exhibits significant efficacies in inhibiting bacterial, viral, and fungal infections, facilitating wound healing, restraining the proliferation of cancers, and ameliorating psoriatic or vitiligous lesions. This review summarizes recent advances in CAP therapies for various skin diseases and implicates future strategies for increasing effectiveness or broadening clinical indications.

Clinical efficacy and safety of Qingshu Yiqi decoction as a complementary and alternative therapy for COVID-19 with Delta variant: A protocol for systematic review and meta-analysis.

BACKGROUND: Qingshu Yiqi decoction combined with general western medicine are important and prevalent recently treatment method of corona virus disease 2019 (COVID-19) with Delta variant, but the efficacy and safety were not clear. This meta-analysis aims to clarify their clinical efficacy and safety thus to provide evidence for clinical application. METHODS: We searched Chinese databases CNKI, Wanfang, VIP and English databases PubMed, Cochrane Library, Embase for the current study. The retrieval time was from the establishment to November, 2021. Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network. RevMan 5.3 and Stata 12.0 were used to perform this research. RESULTS: The efficacy and safety of Qingshu Yiqi decoction combined with western medicine for COVID-19 with Delta variant were evaluated in terms of total effective rate, TCM syndrome score, negative conversation rate of viral nucleic acid, disappearance rate of clinical symptoms (such as fever, cough, and fatigue), CT improvement, white blood cell (WBC), lymphocyte (LYM) and adverse reaction rate. CONCLUSION: This study provides reliable evidence-based support for the clinical efficacy and safety of Qingshu Yiqi decoction as a complementary and alternative therapy for COVID-19 with Delta variant. PROSPERO REGISTRATION NUMBER: CRD42021271606.

Factors Affecting Perceived Health Benefits and Use Behaviors in Urban Green Spaces During the COVID-19 Pandemic in Southern China Megacities.

Background: The COVID-19 pandemic has alienated people from urban green spaces (UGSs) that have various health outcomes for humans. However, little is known about the influential factors of perceived health benefits and use behaviors in UGSs during the COVID-19 pandemic. This study aims to explore the key factors that influence perceived health benefits and use behaviors in UGSs and to assess the mediating role of place attachment in relationships during the COVID-19 pandemic in Chinese megacities. Methods: We conducted an online questionnaire survey from December 2020 to March 2021 in Guangzhou and Shenzhen, China. Six multiple regression models were constructed to investigate the main factors by which UGSs influence citizens' perceived health benefits and use behaviors. Four mediation models were established using the structural equation modeling (SEM) method to explore the mediating effect of place attachment. Results: A total of 628 questionnaires were included in the analysis. The results revealed that some UGS components (green space access, maintenance, and soundscape) significantly affected perceived health benefits for citizens (physical, mental, and social health) during the COVID-19 pandemic. Conversely, use behaviors (frequency of visits, duration of visits, and activity intensity) were mainly affected by the sociodemographic context but less affected by UGS components. In addition, UGS components were found to significantly predict place attachment, which in turn influenced the perceived health benefits, frequency, and duration of visits. Conclusions: This study distinguished the key factors that affect perceived health benefits and use behaviors during the COVID-19 pandemic: green space access, maintenance, soundscape, and sociodemographic characteristics. Place attachment still needs to be considered when discussing how to encourage citizens to visit UGSs during the pandemic. These findings provide implications for policymakers and landscape planners regarding design and management measures for UGSs that are conducive to coping with pandemics.

Haplotype-resolved de novo assembly of the Vero cell line genome.

The Vero cell line is the most used continuous cell line for viral vaccine manufacturing with more than 40 years of accumulated experience in the vaccine industry. Additionally, the Vero cell line has shown a high affinity for infection by MERS-CoV, SARS-CoV, and recently SARS-CoV-2, emerging as an important discovery and screening tool to support the global research and development efforts in this COVID-19 pandemic. However, the lack of a reference genome for the Vero cell line has limited our understanding of host-virus interactions underlying such affinity of the Vero cell towards key emerging pathogens, and more importantly our ability to redesign high-yield vaccine production processes using Vero genome editing. In this paper, we present an annotated highly contiguous 2.9 Gb assembly of the Vero cell genome. In addition, several viral genome insertions, including Adeno-associated virus serotypes 3, 4, 7, and 8, have been identified, giving valuable insights into quality control considerations for cell-based vaccine production systems. Variant calling revealed that, in addition to interferon, chemokines, and caspases-related genes lost their functions. Surprisingly, the ACE2 gene, which was previously identified as the host cell entry receptor for SARS-CoV and SARS-CoV-2, also lost function in the Vero genome due to structural variations.

The Impact of the COVID-19 on the Insurance Industry in China

The sudden advent of COVID-19 brought a huge impact on China's insurance industry, including the nation's social medical insurance and commercial insurance. As the central government published a strict quarantine policy to contain the spread of COVID-19, nearly all of business units stagnated. The deteriorating economic situation decreased income of both companies and employees and increased the unemployment rate, which directly led the income of China's insurance industry to slump during COVID-19. However, as the epidemic had been largely contained, the central government reopened the economy. The rapid and strong recovery of domestic economy built a solid foundation for Chinese insurance industry's income to rebound in the long term. COVID- 19 had a great influence on the expenditure of insurance industry as well. The policies of The BUREAU of Health Insurance might lead social insurance expenditures to greatly increase during the epidemic. Meanwhile the expenditures of commercial insurance did not increase or may even decreased because there is a risk of lawsuit in business interruption and director and officers' insurance. Moreover, COVID-19 also negatively influenced the investment amount and income of commercial insurance companies because the investment income of social insurance may be affected mainly by the currency inflation during the epidemic. In fact, COVID-19 revealed that there is still a long way for Chinese insurance industry to go before we could truly build a leading insurance system that is driven by science and technology: more stable in its development, more efficient in its operation and more comprehensive in its coverage and better in its system. However, the sudden outbreak of the epidemic would directly promote the reform of the industry in multiple-leveled fields and thus accelerate the establishment of new future-oriented insurance companies.

A metagenomic-based method to study hospital air dust resistome.

As a symbol of the defense mechanisms that bacteria have evolved over time, the genes that make bacteria resist antibiotics are overwhelmingly present in the environment. Currently, bacterial antibiotic resistance genes (ARGs) in the air are a serious concern. Previous studies have identified bacterial communities and summarized putative routes of transmissions for some dominant hospital-associated pathogens from hospital indoor samples. However, little is known about the possible indoor air ARG transportation. In this study, we mainly surveyed air-conditioner air dust samples under different airflow conditions and analyzed these samples using a metagenomic-based method. The results show air dust samples exhibited a complex resistome, and the average concentration is 0.00042 copies/16S rRNA gene, which is comparable to some other environments. The hospital air-conditioners can form resistome over time and accumulate pathogens. In addition, our results indicate that the Outpatient hall is one of the main ARG transmission sources, which can distribute ARGs to other departments (explains >80% resistome). We believe that the management should focus on ARG carrier genera such as Staphylococcus, Micrococcus, Streptococcus, and Enterococcus in this hospital and our novel evidence-based network strategy proves that plasmid-mediated ARG transfer can occur frequently. Overall, these results provide insights into the characteristics of air dust resistome and possible route for how ARGs are spread in air.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: A Multicenter Study (preprint)

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from Jan 17 to Feb 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920 (95% confidence interval : 0.902-0.938; AUROC=0.915, and its standard deviation of 0.028, as evaluated in 5-fold cross-validation). At a value of whether the predicted score >4.0, the model could detect NCP with a specificity of 98.3%; at a cut-off value of < -0.5, the model could rule out NCP with a sensitivity of 97.9%. The study demonstrated that the rapid screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

Host susceptibility to severe COVID-19: a retrospective analysis of 487 case outside Wuhan (preprint)

Background: The recent outbreak of SARS-CoV-2 infection results in a considerable morbidity and mortality, mainly in China. The study is to investigate the intrinstic features of infected patients that associated with severe type of this disease. Method: A total of 487 laboratory-confirmed COVID-19 patients were included in analysis. The demographic and epidemiological of patients representing as mild and severe at admission were compared. A step-wise multivariate logistic regression analysis were performed to identify significant risk factors associated with severe COVID-19 . A score systemc incorporating risk factors was established for risk stratification and validated in a small cohort during in-hospital follow-up. Results: Of all patients, 49 (10.1%) cases are severe at admission. Severe cases are elder [56(17) vs. 45(19), P<0.001), with more male (73.5% vs. 50.9%, P=0.003). They have a higher incidence of hypertension (53.1% vs. 16.7%, P<0.001), diabetes (14.3% vs. 5.0%, P=0.009), cardiovascular diseases (8.2% vs. 1.6%, P=0.003) and malignancy (4.1% vs. 0.7%, P=0.025), and less exposure to epidemic area (49.0% vs. 65.1%, P=0.027), but more infected familiy members(P=0.031). On multivariate analysis, elder age, male and presence of hypertension are independently associated with severe disease at admission. A host risk score, incorporating age, sex and hypertension history, clearly stratifies risk of developing severe type of COVID-19 both in patients at admission and during in-hospital follow-up. Conclusions: Elder age, male and presence of hypertension are associated with host susceptibility to developing severe COVID-19. The host risk score may be a useful tool to identify high risk indiviuals but requires validation.