Heparan sulfate promotes ACE2 super-cluster assembly to enhance SARS-CoV-2-associated syncytium formation.

The mechanism of syncytium formation, caused by spike-induced cell-cell fusion in severe COVID-19, is largely unclear. Here we combine chemical genetics with 4D confocal imaging to establish the cell surface heparan sulfate (HS) as a critical host factor exploited by SARS-CoV-2 to enhance spike’s fusogenic activity. HS binds spike to facilitate ACE2 clustering, generating synapse-like cell-cell contacts to promote fusion pore formation. ACE2 clustering, and thus, syncytium formation is significantly mitigated by chemical or genetic elimination of cell surface HS, while in a cell-free system consisting of purified HS, spike, and lipid-anchored ACE2, HS directly induces ACE2 clustering. Importantly, the interaction of HS with spike allosterically enables a conserved ACE2 linker in receptor clustering, which concentrates spike at the fusion site to overcome fusion-associated activity loss. This fusion-boosting mechanism can be effectively targeted by an investigational HS-binding drug, which reduces syncytium formation in vitro and viral infection in mice.

Duration of viable virus shedding and polymerase chain reaction positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract: a systematic review and meta-analysis.

OBJECTIVES: To assess the duration of viable virus shedding and polymerase chain reaction (PCR) positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract. METHODS: We systematically searched PubMed, Cochrane, and Web of Science for original articles reporting the duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract from November 11, 2021 to December 11, 2022. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO (CRD42022357349). We used the DerSimonian-Laird random-effects meta-analyses to obtain the pooled value and the 95% confidence intervals. RESULTS: We included 29 studies and 230,227 patients. The pooled duration of viable virus shedding of the SARS-CoV-2 Omicron variant in the upper respiratory tract was 5.16 days (95% CI: 4.18-6.14), and the average duration of PCR positivity was 10.82 days (95% CI: 10.23-11.42). The duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in symptomatic patients was slightly higher than that in asymptomatic patients, but the difference was not significant (P >0.05). CONCLUSION: The current study improves our understanding of the status of the literature on the duration of viable virus shedding and PCR positivity of Omicron in the upper respiratory tract. Our findings have implications for pandemic control strategies and infection control measures.

Duration of SARS-CoV-2 Serum-Neutralizing Antibodies Against SARS-CoV-2 Dependent on the Individual.

We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.

Immunogenicity, effectiveness, and safety of COVID-19 vaccines among children and adolescents aged 2-18 years: an updated systematic review and meta-analysis.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need for safe and effective COVID-19 vaccines to protect children and adolescents. This study aims to provide scientific evidence and recommendations for the application of COVID-19 vaccines in children and adolescents by analyzing the latest studies. METHODS: We systematically searched MEDLINE (accessed through PubMed), Embase, and Web of Science from January 1, 2020, to October 8, 2022. Eligible clinical trials, cohort studies, case‒control studies, and cross-sectional studies with extractable data were included in immunogenicity, effectiveness, and safety analyses. According to the heterogeneity, we chose a fixed-effect model (when I2 ≤ 50) or a random-effects model (when I2 > 50) to pool effect values. RESULTS: A total of 88 articles were included. The seroconversion rates after the first, second, and third doses of the vaccines were 86.10%, 96.52%, and 99.87%, respectively. After the first and second doses, vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 infection was 42.87% [95% confidence interval (CI) = 27.09%-58.65%] and 63.33% (95% CI = 52.09%-74.56%), respectively. After the first and second doses, VE against COVID-19 was 60.65% (95% CI = 44.80%-76.50%) and 75.77% (95% CI = 63.99%-87.56%), respectively. VE against hospitalization due to COVID-19 after the first and second doses was 72.74% (95% CI = 51.48%-94.01%) and 82.78% (95% CI = 75.78%-89.78%), respectively. The most common adverse events were injection site pain, fatigue/asthenia/tiredness, headache, myalgia/muscle pain, and chills. The incidence rate of myocarditis or pericarditis was 2.42/100,000 people. In addition, the subgroup analysis showed that children aged ≤ 5 years had the lowest incidence of adverse events, and the incidence rate of adverse events was higher for mRNA vaccines than for inactivated vaccines. CONCLUSIONS: COVID-19 vaccines have good immunogenicity, effectiveness, and safety among children and adolescents. We recommend that children and adolescents be vaccinated as soon as possible to protect them and slow the spread of COVID-19.

Fast and Sensitive Detection of SARS-CoV-2 Nucleic Acid Using a Rapid Detection System Free of RNA Extraction.

Objectives: To establish and evaluate the analytical and clinical performance of the Flash20 SARS-CoV-2 nucleic acid rapid detection system free of RNA extraction. Methods: The limit of detection (LoD) was determined using a negative nasopharyngeal swab matrix spiked with different concentrations of SARS-CoV-2 virus; a total of 734,337 reference sequences of viral genomes from GenBank were used for the in-silico analysis to assess the inclusivity of the assay. The specificity of the system was evaluated by testing 27 medically relevant organisms. A total of 115 clinical specimens were collected and tested on the Flash20 SARS-CoV-2 detection system and with an FDA-approved comparator test to assess the clinical performance of the system. Results: The LoD of the Flash20 SARS-CoV-2 detection system is 250 copies/mL with a positive rate ≥90% (n = 20); alignments results showed that over 99% identity of the primer and probe of the Flash20 SARS-CoV-2 nucleic acid rapid detection system to the available SARS-CoV-2 sequences; the omicron samples tested 100% positive. None of the 27 organisms showed cross-reactivity with the Flash20 SARS-CoV-2 nucleic acid rapid detection system. Among all the 215 clinical samples, the Flash20 SARS-CoV-2 nucleic acid rapid detection system exhibits a high sensitivity of 99.24% (131/132) and 100% (83/83) specificity. Conclusion: The nucleic acid rapid detection system provides sensitive and accurate detection of SARS-CoV-2 free of RNA extraction. The high sensitivity and short time to results of approximately 35 minutes may impact earlier infection control and disease management.

Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects.

Introduction: An approach toward novel neutralizing IgY polyclonal antibodies (N-IgY-pAb) against SARS-CoV-2 S-ECD was developed. Material and methods: The novel N-IgY-pAb and its intranasal spray response against the wild type ("'WH-Human 1") SARS-CoV-2 virus, variants of Delta or Omicron were up to 98%. Unique virus peptides binding to N-IgY-pAb were screened by a SARS-CoV-2 proteome microarray. Results: Seventeen mutation-free peptides with a Z-score > 3.0 were identified as potent targets from a total of 966 peptides. The new findings show that one is in the RBM domain (461LKPFERDISTEIYQA475 ), two are in the NTD domain (21RTQLPPAYTNSFTRG35, 291CALDPLSETKCTLKS305) four are in the C1/2-terminal (561PFQQFGRDIADTTDA575,571DTTDAVRDPQTLEIL585,581TLEILDITPCSFGGV595, 661ECDIPIGAGICASYQ675 ), three are in the S1/S2 border (741YICGDSTECSNLLLQ755, 811KPSKRSFIEDLLFNK825, 821LLFNKVTLADAGFIK835) one target is in HR2 (1161SPDVDLGDISGINAS1175) and one is in HR2-TM (1201QELGKYEQYIKWPWY1215). Moreover, five potential peptides were in the NSP domain: nsp3-55 (1361SNEKQEILGTVSWNL1375), nsp14-50 (614HHANEYRLYLDAYNM642, ORF10-3 (21MNSRNYIAQVDVVNFNLT38, ORF7a-1(1MKIILFLALITLATC15) and ORF7a-12 (1116TLCFTLKRKTE121). Discussion and conclusion: We concluded that the N-IgY-pAb could effectively neutralize the SARS-CoV-2. The new findings of seventeen potent conserved peptides are extremely important for developing new vaccines and "cocktails" of neutralizing Abs for efficient treatments for patients infected with SARS-CoV-2.

Effect of COVID-19 Vaccines on Reducing the Risk of Long COVID in the Real World: A Systematic Review and Meta-Analysis.

The coronavirus disease 2019 (COVID-19) is still in a global pandemic state. Some studies have reported that COVID-19 vaccines had a protective effect against long COVID. However, the conclusions of the studies on the effect of COVID-19 vaccines on long COVID were not consistent. This study aimed to systematically review relevant studies in the real world, and performed a meta-analysis to explore the relationship between vaccination and long COVID. We systematically searched PubMed, Embase, Web of science, and ScienceDirect from inception to 19 September 2022. The PICO (P: patients; I: intervention; C: comparison; O: outcome) was as follows: patients diagnosed with COVID-19 (P); vaccination with COVID-19 vaccines (I); the patients were divided into vaccinated and unvaccinated groups (C); the outcomes were the occurrence of long COVID, as well as the various symptoms of long COVID (O). A fixed-effect model and random-effects model were chosen based on the heterogeneity between studies in order to pool the effect value. The results showed that the vaccinated group had a 29% lower risk of developing long COVID compared with the unvaccinated group (RR = 0.71, 95% CI: 0.58-0.87, p < 0.01). Compared with patients who were not vaccinated, vaccination showed its protective effect in patients vaccinated with two doses (RR = 0.83, 95% CI: 0.74-0.94, p < 0.01), but not one dose (RR = 0.83, 95% CI: 0.65-1.07, p = 0.14). In addition, vaccination was effective against long COVD in patients either vaccinated before SARS-CoV-2 infection/COVID-19 (RR = 0.82, 95% CI: 0.74-0.91, p < 0.01) or vaccinated after SARS-CoV-2 infection/COVID-19 (RR = 0.83, 95% CI: 0.74-0.92, p < 0.01). For long COVID symptoms, vaccination reduced the risk of cognitive dysfunction/symptoms, kidney diseases/problems, myalgia, and sleeping disorders/problems sleeping. Our study shows that COVID-19 vaccines had an effect on reducing the risk of long COVID in patients vaccinated before or after SARS-CoV-2 infection/COVID-19. We suggest that the vaccination rate should be improved as soon as possible, especially for a complete vaccination course. There should be more studies to explore the basic mechanisms of the protective effect of COVID-19 vaccines on long COVID in the future.

Immunogenicity and Safety of COVID-19 Vaccines among People Living with HIV: A Systematic Review and Meta-Analysis.

BACKGROUND: The immunogenicity and safety of COVID-19 vaccines among people living with human immunodeficiency virus (PLWH) are unclear. We aimed to evaluate the immunogenicity and safety of COVID-19 vaccines among PLWH. METHODS: We systematically searched PubMed, EMBASE, and Web of Science from 1 January 2020 to 28 April 2022 and included observational studies, randomized clinical trials, and non-randomized clinical trials reporting extractable data about the immunogenicity and safety of COVID-19 vaccines among PLWH. RESULTS: A total of 34 eligible studies covering 4517 PLWH were included. The pooled seroconversion rates among PLWH after the first and second doses were 67.51% (95% confident interval (CI) 49.09-85.93%) and 96.65% (95%CI 95.56-97.75%), respectively. The seroconversion was similar between PLWH and healthy controls after the first (risk ratio (RR) = 0.89, 95%CI 0.76-1.04) and the second (RR = 0.97, 95%CI 0.93-1.00) dose. Moreover, the geometric mean titer (GMT) showed no significant difference between PLWH and healthy controls after the first dose (standardized mean difference (SMD) = 0.30, 95%CI -1.11, 1.70) and the second dose (SMD = -0.06, 95%CI -0.18, 0.05). Additionally, the pooled incidence rates of total adverse events among PLWH after the first and the second dose were 46.55% (95%CI 28.29-64.82%) and 30.96% (95%CI 13.23-48.70%), respectively. There was no significant difference in risks of total adverse events between PLWH and healthy controls after the first (RR = 0.86, 95%CI 0.67-1.10) and the second (RR = 0.88, 95%CI 0.68-1.14) dose. CONCLUSIONS: The available evidence suggested that the immunogenicity and safety of COVID-19 vaccines among PLWH were acceptable. There was no significant difference in the seroconversion rates and incidence rates of adverse events of COVID-19 vaccines between PLWH and healthy controls.

Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth.

One major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce emergence of antibody resistance. Here we engineer two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv)2 design (14-H-06) but not the CrossMAb design (14-crs-06) shows increased antigen-binding and virus-neutralizing activities against multiple SARS-CoV-2 variants as well as increased breadth of neutralizing activity compared to the cocktail. X-ray crystallography and cryo-EM reveal distinct binding models for individual cocktail antibodies, and computational simulations suggest higher inter-spike crosslinking potentials by 14-H-06 than 14-crs-06. In mouse models of infections by SARS-CoV-2 and multiple variants, 14-H-06 exhibits higher or equivalent therapeutic efficacy than the cocktail. Rationally engineered bsAbs represent a cost-effective alternative to antibody cocktails and a promising strategy to improve potency and breadth.

Multiomic analysis reveals cell-type-specific molecular determinants of COVID-19 severity.

The determinants of severe COVID-19 in healthy adults are poorly understood, which limits the opportunity for early intervention. We present a multiomic analysis using machine learning to characterize the genomic basis of COVID-19 severity. We use single-cell multiome profiling of human lungs to link genetic signals to cell-type-specific functions. We discover >1,000 risk genes across 19 cell types, which account for 77% of the SNP-based heritability for severe disease. Genetic risk is particularly focused within natural killer (NK) cells and T cells, placing the dysfunction of these cells upstream of severe disease. Mendelian randomization and single-cell profiling of human NK cells support the role of NK cells and further localize genetic risk to CD56bright NK cells, which are key cytokine producers during the innate immune response. Rare variant analysis confirms the enrichment of severe-disease-associated genetic variation within NK-cell risk genes. Our study provides insights into the pathogenesis of severe COVID-19 with potential therapeutic targets.

Changes in lifestyles and depressive symptom among patients with chronic diseases during COVID-19 lockdown.

This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs (noncommunicable diseases). We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8-16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown. A total of 3327 participants were included in the COVID-19 survey, including 2098 (63.1%) reported having NCDs at baseline and 1457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9 to 13.5%, and poor sleepers from 23.9 to 15.3%, while low physical activity increased from 13.4 to 25.2%, among participants with NCDs (P < 0.05 for all comparisons using McNemar's test). Participants with NCDs were more likely than those without to have depressive symptom (OR, 1.30; 95% CI 1.05-1.61), especially among those who need to refill their medication during the COVID-19 lockdown (OR, 1.52; 95% CI 1.15-2.02). Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown.

Percentage of Asymptomatic Infections among SARS-CoV-2 Omicron Variant-Positive Individuals: A Systematic Review and Meta-Analysis.

BACKGROUND: Asymptomatic infections are potential sources of transmission for coronavirus disease 2019, especially during the epidemic of the SARS-CoV-2 Omicron variant. We aimed to assess the percentage of asymptomatic infections among SARS-CoV-2 Omicron variant-positive individuals detected by gene sequencing or specific polymerase chain reaction (PCR). METHODS: We searched PubMed, EMBASE, and Web of Science from 26 November 2021 to 13 April 2022. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO (CRD42022327894). Three researchers independently extracted data and two researchers assessed quality using pre-specified criteria. The pooled percentage with 95% confidence interval (CI) of asymptomatic infections of SARS-CoV-2 Omicron was estimated using random-effects models. RESULTS: Our meta-analysis included eight eligible studies, covering 7640 Omicron variant-positive individuals with 2190 asymptomatic infections. The pooled percentage of asymptomatic infections was 32.40% (95% CI: 25.30-39.51%) among SARS-CoV-2 Omicron variant-positive individuals, which was higher in the population in developing countries (38.93%; 95% CI: 19.75-58.11%), with vaccine coverage ≥ 80% (35.93%; 95% CI: 25.36-46.51%), with a travel history (40.05%; 95% CI: 7.59-72.51%), community infection (37.97%; 95% CI: 10.07-65.87%), and with a median age < 20 years (43.75%; 95% CI: 38.45-49.05%). CONCLUSION: In this systematic review and meta-analysis, the pooled percentage of asymptomatic infections was 32.40% among SARS-CoV-2 Omicron variant-positive individuals. The people who were vaccinated, young (median age < 20 years), had a travel history, and were infected outside of a clinical setting (community infection) had higher percentages of asymptomatic infections. Screening is required to prevent clustered epidemics or sustained community transmission caused by asymptomatic infections of Omicron variants, especially for countries and regions that have successfully controlled SARS-CoV-2.

Graph Convolutional Network-Based Screening Strategy for Rapid Identification of SARS-CoV-2 Cell-Entry Inhibitors.

The cell entry of SARS-CoV-2 has emerged as an attractive drug development target. We previously reported that the entry of SARS-CoV-2 depends on the cell surface heparan sulfate proteoglycan (HSPG) and the cortex actin, which can be targeted by therapeutic agents identified by conventional drug repurposing screens. However, this drug identification strategy requires laborious library screening, which is time consuming, and often limited number of compounds can be screened. As an alternative approach, we developed and trained a graph convolutional network (GCN)-based classification model using information extracted from experimentally identified HSPG and actin inhibitors. This method allowed us to virtually screen 170,000 compounds, resulting in ∼2000 potential hits. A hit confirmation assay with the uptake of a fluorescently labeled HSPG cargo further shortlisted 256 active compounds. Among them, 16 compounds had modest to strong inhibitory activities against the entry of SARS-CoV-2 pseudotyped particles into Vero E6 cells. These results establish a GCN-based virtual screen workflow for rapid identification of new small molecule inhibitors against validated drug targets.

Effectiveness and Safety of SARS-CoV-2 Vaccines among Children and Adolescents: A Systematic Review and Meta-Analysis.

BACKGROUND: The proportion of children and adolescents with COVID-19 had gradually increased according to data reported by WHO. However, there was no meta-analysis of effectiveness and safety of SARS-CoV-2 vaccines in children and adolescents. We aimed to provide investigation-based medical evidence and reference recommendations for children and adolescents in regard to SARS-CoV-2 vaccines. METHODS: We systematically searched PubMed, Embase, and Web of Science from inception to 5 January 2022. RCTs and observational studies that examined the effectiveness and safety were included. RESULTS: A total of 13 eligible studies were included for analysis. For the first dose, the effectiveness of SARS-CoV-2 vaccines against SARS-CoV-2 infection and COVID-19 was 88.5% (95% CI:15.7-98.4%, p = 0.033) and 84.3% (95% CI: 66.6-92.6%, p < 0.001) separately. For the second dose, the effectiveness against SARS-CoV-2 infection and COVID-19 was 91.6% (95% CI: 37.8-99.5%, p = 0.083) and 92.7 (95% CI: 82.2-97.0, p < 0.001) separately. Injection-site pain, fatigue, headache, anorexia, and axillary swelling were the top five adverse events after the first dose of SARS-CoV-2 vaccines. Fatigue, injection-site pain, headache, chills, and myalgia/muscle pain were the top five adverse events after the second dose of SARS-CoV-2 vaccines. CONCLUSIONS: SARS-CoV-2 vaccines had good effectiveness and safety in children and adolescents. We suggest that children and adolescents should get vaccinated as soon as possible to protect themselves and slow the spread of the pandemic.

RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants.

With the rapid emergence and spread of SARS-CoV-2 variants, development of vaccines with broad and potent protectivity has become a global priority. Here, we designed a lipid nanoparticle-encapsulated, nucleoside-unmodified mRNA (mRNA-LNP) vaccine encoding the trimerized receptor-binding domain (RBD trimer) and showed its robust capability in inducing broad and protective immune responses against wild-type and major variants of concern (VOCs) in the mouse model of SARS-CoV-2 infection. The protectivity was correlated with RBD-specific B cell responses especially the long-lived plasma B cells in bone marrow, strong ability in triggering BCR clustering, and downstream signaling. Monoclonal antibodies isolated from vaccinated animals demonstrated broad and potent neutralizing activity against VOCs tested. Structure analysis of one representative antibody identified a novel epitope with a high degree of conservation among different variants. Collectively, these results demonstrate that the RBD trimer mRNA vaccine serves as a promising vaccine candidate against SARS-CoV-2 variants and beyond.

The impact of cross-border knowledge management on internationalizing Renminbi: lessons from the belt and road initiative

PurposeIn the process of Renminbi (RMB) internationalization, the heterogeneity and complexity in knowledge under the multicultural contexts have been considered as important factors that can have profound impacts on the cross-border flow of the RMB currency. Moreover, COVID-19, an exogenous shock, also triggers more in-depth reflection on the relationship between cross-border knowledge management and the financial risk governance. In addition, the needs to effectively respond to global risks and crises prompt the necessity in systematically establishing an effective cross-border knowledge management mechanism and innovatively solidifying the knowledge bases needed for the further internationalization of the RMB.Design/methodology/approachBased on the analysis on the current status of the RMB internationalization, this paper qualitatively explores some major challenges and difficulties encountered in the process of RMB internationalization from the perspectives of knowledge management and cross-cultural theories. To effectively mitigate these challenges and difficulties, discussions and recommendations centered on three main aspects: cross-cultural management;cognition;and innovation for the further development of the RMB internationalization are also presented in this paper.FindingsBased on the analysis on the cross-border knowledge management and cross-cultural perspectives, this paper identifies three major challenges and difficulties that the RMB internationalization is encountering, including: cultural heterogeneity and its adverse impacts on the communication amongst economic entities;the existence of knowledge iceberg;and the difficulty it presents to cognition and financial innovation. Meanwhile, the authors also present recommendations on the development of the cross-border knowledge management mechanism for furthering the progress of internationalizing the RMB currency.Research limitations/implicationsFrom the perspective of cross-border knowledge management, this study not only elaborates on the recommendations aimed at further promoting the RMB internationalization but also provides reference and guidance for the state, central banks and commercial banks to play better roles in furthering the RMB internationalization.Originality/valueThis paper creatively integrates the micro knowledge management into the macro process of RMB internationalization, thoroughly discusses two main challenges and difficulties encountered in the process of RMB internationalization from the unique perspective of cross-border knowledge management under the multicultural contexts and provides relevant recommendations for RMB’s further internationalization. This study also enriches the exploration of knowledge management outcome variables and further expands the research field of knowledge management.

The Role of Pulmonary Surfactants in the Treatment of Acute Respiratory Distress Syndrome in COVID-19.

Lung alveolar type-II (AT-II) cells produce pulmonary surfactant (PS), consisting of proteins and lipids. The lipids in PS are primarily responsible for reducing the air-fluid surface tension inside the alveoli of the lungs and to prevent atelectasis. The proteins are of two types: hydrophilic and hydrophobic. Hydrophilic surfactants are primarily responsible for opsonisation, thereby protecting the lungs from microbial and environmental contaminants. Hydrophobic surfactants are primarily responsible for respiratory function. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters the lungs through ACE-2 receptors on lungs and replicates in AT-II cells leading to the etiology of Coronavirus disease - 2019 (COVID-19). The SARS-CoV-2 virus damages the AT-II cells and results in decreased production of PS. The clinical symptoms of acute respiratory distress syndrome (ARDS) in COVID-19 patients are like those of neonatal respiratory distress syndrome (NRDS). The PS treatment is first-line treatment option for NRDS and found to be well tolerated in ARDS patients with inconclusive efficacy. Over the past 70°years, a lot of research is underway to produce natural/synthetic PS and developing systems for delivering PS directly to the lungs, in addition to finding the association between PS levels and respiratory illnesses. In the present COVID-19 pandemic situation, the scientific community all over the world is searching for the effective therapeutic options to improve the clinical outcomes. With a strong scientific and evidence-based background on role of PS in lung homeostasis and infection, few clinical trials were initiated to evaluate the functions of PS in COVID-19. Here, we connect the data on PS with reference to pulmonary physiology and infection with its possible therapeutic benefit in COVID-19 patients.

Association between tachyarrhythmia and mortality in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19).

BACKGROUND: Cardiovascular involvement manifesting as arrhythmias has been confirmed in patients with coronavirus disease 2019 (COVID-19), so we aimed to explore the association between primary tachyarrhythmia and death in critically ill patients with COVID-19 in this retrospective study. METHODS: A total of 79 critically ill patients with COVID-19 were included. Demographic characteristics, clinical data (past history, vital signs, therapeutic management, and outcomes), and results of laboratory findings and cardiac investigations were collected. All statistical analyses were performed using SPSS 23.0 software (IBM, Armonk, NY, USA). RESULTS: The median age was 65±12 years, and 53 patients (67%) were male. A total of 57 (72%) patients died, and compared with survivors, these patients were older and had significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score and fewer lymphocytes as well as higher heart rate (P<0.05). Autopsy findings did not suggest severe myocarditis. A total of 19 (24%) patients had tachyarrhythmias, including 10 (13%) with atrial fibrillation (AF) and 9 (11%) with ventricular tachycardia or fibrillation. The incidence of tachyarrhythmias in non-survivor was much higher than in survivors (P=0.04). In a Cox regression model, older patients with ventricular tachyarrhythmias (VTAs) age were at a higher risk of death, with hazard ratio (HR) of 3.302 [95% confidence interval (CI), 1.524-7.154, P=0.002] and 1.045 (95% CI, 1.020-1.071, P=0.000), respectively. The use of beta-blockers [HR, 0.219 (95% CI, 0.066-0.722); P=0.013] was associated with a lower risk of death. CONCLUSIONS: Critically ill patients with COVID-19 had a poor prognosis. VTA and older age were independent prognostic factors of death. Beta-blockers might be an effective therapy to improve survival.