Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection.

Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitors, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, block respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We used a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptides to the respiratory tract and demonstrated the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevented MeV infection, resulting in the complete absence of MeV RNA, MeV-infected cells, and MeV-specific humoral responses in treated animals. This strategy provides an additional shield which complements vaccination to fight against respiratory infection, presenting a proof-of-concept for the aerosol delivery of fusion inhibitory peptides to protect against measles and other airborne viruses, including SARS-CoV-2, in case of high-risk exposure, that can be readily translated to human trials.

Drivers of High Concentrations of Secondary Organic Aerosols in Northern China during the COVID-19 Lockdowns.

During the COVID-19 lockdown in early 2020, observations in Beijing indicate that secondary organic aerosol (SOA) concentrations increased despite substantial emission reduction, but the reasons are not fully explained. Here, we integrate the two-dimensional volatility basis set into a state-of-the-art chemical transport model, which unprecedentedly reproduces organic aerosol (OA) components resolved by the positive matrix factorization based on aerosol mass spectrometer observations. The model shows that, for Beijing, the emission reduction during the lockdown lowered primary organic aerosol (POA)/SOA concentrations by 50%/18%, while deteriorated meteorological conditions increased them by 30%/119%, resulting in a net decrease in the POA concentration and a net increase in the SOA concentration. Emission reduction and meteorological changes both led to an increased OH concentration, which accounts for their distinct effects on POA and SOA. SOA from anthropogenic volatile organic compounds and organics with lower volatility contributed 28 and 62%, respectively, to the net SOA increase. Different from Beijing, the SOA concentration decreased in southern Hebei during the lockdown because of more favorable meteorology. Our findings confirm the effectiveness of organic emission reductions and meanwhile reveal the challenge in controlling SOA pollution that calls for large organic precursor emission reductions to rival the adverse impact of OH increase.

Clinical characteristics and molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in China, 2017 to 2019: A multicentre prospective observational study.

Human metapneumovirus (HMPV) infection is one of the leading causes of hospitalization in young children with acute respiratory illness. In this study, we prospectively collected respiratory tract samples from children who were hospitalized with acute lower respiratory tract infection in six hospitals in China from 2017 to 2019. HMPV was detected in 145 out of 2733 samples (5.3%) from the hospitalized children. The majority of HMPV-positive children were under the age of two (67.6%), with a median age of one year. HMPV can independently cause acute lower respiratory tract infection in young children, while all patients showed mild clinical symptoms. Of all the co-infected patients, HMPV was most commonly detected with enterovirus (EV) or rhinovirus (RhV) (38.0%, followed by respiratory syncytial virus (RSV) (32.0%). The highest detection rate occurred from March to May in both northern and southern China. Out of 145 HMPV positive samples, 48 were successfully typed, of which 36 strains were subgrouped into subtypes A2c (75%), eight strains were included in subtype B1 (16.7%), and four strains were included in subtype B2 (8.3%). Moreover, 16 A2c strains contained 111-nucleotide duplications in the G gene. Twenty-seven complete HMPV genomes were successfully obtained, and 25 (92.6%) strains belonged to subtype A2c, whereas one strain was included in subgroup B1 and another was included in subgroup B2. A total of 277 mutations were observed in the complete genomes of 25 A2c strains. All results presented here improve our understanding of clinical characteristics and molecular epidemiology of HMPV infection in children.

SARS-CoV-2 Omicron subvariants exhibit distinct fusogenicity, but similar sensitivity, to pan-CoV fusion inhibitors.

Continuous emergence of the Omicron variant, along with its subvariants, has caused an increasing number of infections, reinfections, and vaccine-breakthrough infections, seriously threatening human health. Recently, several new Omicron subvariants, such as BA.5, BA.2.75, BA.4.6, and BF.7, bearing distinct mutation profiles in their spike (S) proteins, have significantly increased their capacity to evade vaccine-induced immunity and have shown enhanced infectivity and transmissibility, quickly becoming dominant sublineages. In this study, we found the S proteins of these Omicron subvariants to have 2- to 4-fold more efficient membrane fusion kinetics than that of the original Omicron variant (BA.1), indicating that these novel Omicron subvariants might possess increased pathogenicity. We also identified that peptide-based pan-CoV fusion inhibitors, EK1 and EK1C4, showed equal efficacy against membrane fusion mediated by S proteins of the noted Omicron subvariants and infection by their pseudoviruses. Additionally, either immune sera induced by wild-type (WT) SARS-CoV-2 RBD-based vaccine or BA.2 convalescent sera showed potent synergism with EK1 against both WT SARS-CoV-2 and various Omicron subvariants, further suggesting that EK1-based fusion inhibitors are promising candidates for development as clinical antiviral agents against the currently circulating Omicron subvariants.

A multicenter study on molecular epidemiology of rhinovirus isolated from children with community acquired pneumonia in China during 2017-2019.

Rhinoviruses (RVs) are a major pathogen of community acquired pneumonia in children. To investigate the prevalence and genetic characteristics of RVs in China, we performed a molecular epidemiological study during 2017-2019 in community acquired pneumonia (CAP) in pediatric patients. In this multicenter study, 109 RV-A, 20 RV-B and 80 RV-C were identified. Among them, RV-A12, RV-A101, RV-A78, RV-A49, RV-A22, RV-B52, RV-C2, RV-C53 and RV-C5 were the common genotypes in the study. A total of 23 complete genome of RVs including 4 RV-A, 1 RV-B and 18 RV-C were obtained. Furthermore, in the RV-C isolates, one RV-C5 and five RV-C53 genotypes were found, which have a limited number in the GenBank. Phylogenetic analysis of the complete genome showed that most of the RVs isolated in the study have high nucleotide sequence identities (>95%) compared with the corresponding reference sequence in the GenBank. In RV-A9, RV-A28, RV-A61 and RV-B52, amino acid mutations were found in the potential neutralizing immunogenic (Nim) sites (Nim-1a and Nim-1b) of the VP1. In RV-B52, one of RV-C2 and RV-C5 isolates, amino acid mutations were found in the P1a peptide of the VP1. However, no recombination events were found in the study. In conclusion, RV-A was the predominant specie of RVs followed by RV-C in the study. The complete genomes of one RV-C5 and five RV-C53 genotypes were obtained which have a limited number sequence in the GenBank. High nucleotide sequence identities (>95%) were found among the complete genome obtained in the study and the corresponding reference sequence in the GenBank. Amino acid mutations were found in the potential Nim-1a, Nim-1b sites and P1a peptide region of the VP1 in parts of RVs.

Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection.

Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitor, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, blocks respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We use a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptide to the respiratory tract and demonstrate the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevents MeV infection, resulting in the complete absence of MeV RNA, MeV-infected cells, and MeV-specific humoral responses in treated animals. This strategy provides an additional means to fight against respiratory infection in non-vaccinated people, that can be readily translated to human trials. It presents a proof-of-concept for the aerosol delivery of fusion inhibitory peptides to protect against measles and other airborne viruses, including SARS-CoV-2, in case of high-risk exposure.

Exploring the self-care practices of social workers in China under the COVID-19 pandemic.

The self-care practices of social workers have garnered increasing attention in the literature, yet little is known about the case of China. To explore the self-care practices of Chinese social workers under the COVID-19 pandemic, this study uses the Self-Care Practice Scale (SCPS) to measure the self-care practices of social workers (N = 1066) in Fujian Province, China. The results indicate that Chinese social workers engage in moderate amounts of self-care practices under the COVID-19 pandemic. Significant group differences exist in social workers' self-care practices by marital status, parenting status, age, health satisfaction, years of practicing social work, average hours of work per day, resignation intention, job satisfaction, number of received supervision services in a year, and self-care education. Significant predictors of self-care include marital status, monthly salary, service status, average hours of work per day, number of received supervision services in a year, school self-care education, job satisfaction, and health satisfaction. This study has practical implications for self-care education and practice, including workplace health promotion and the development of self-care practice policies.

Qualitative suitability test of medical N95 protective mask and subjective evaluation of wearers

OBJECTIVE: To analyze the consistency between the objective and qualitative suitability test results of medical N95 protective masks and the subjective evaluation results of the wearers so as to provide scientific basis for selection of protective masks. METHODS: A survey was conducted among 221 staff in Nanjing COVID-19 designated hospitals from Aug 11, 2021 to Aug 29, 2021. A questionnaire designed by bitterness aerosol method (3 MTMFT-30) approved by Occupational Safety and Health Administration (OSHA) was used to collect and investigate the data on the spot, and the data were statistically analyzed by using SPSS23.0 software. RESULTS: The result of sensitivity test showed that 201 (90.95%) staff passed the test, including 169 (76.47%) staff with grade 1 sensitivity, 30 (13.57%) staff with grade 2 sensitivity and 2(0.90%) staff with grade 3 sensitivity. In terms of objective and qualitative suitability test, the passing rate was 92.04% (185/201), 188 staff passed the first test, 5 staff passed the second test. In terms of the subjective evaluation of the wearers, 111 staff had good subjective overall feeling, accounting for 55.22%;the scores of mouth opening assisted breathing, mask smell and facial muscle adjustment were (2.10+or-0.58) points, (2.13+or-0.42) points and (2.46+or-0.56) points, respectively, significantly lower than (2.55+or-0.50) points of the overall subjective evaluation score, and there was significant difference in the sealing ability of mask before the subjective evaluation and after adjusting by facial muscles (?~2=17.840, P<0.05). The results of objective qualitative suitability test were not consistent with the subjective evaluation of the wearers, and the kappa value was 0.174 (P< 0.001). CONCLUSION: In the objective and qualitative suitability test, the medical N95 protective mask has high safety performance. On the basis of good suitability, it can increase the wearing comfort of the mask, improve the overall subjective evaluation of the wearer, and make full use of the test results to reasonably select and effectively use the protective mask.

SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl- accumulation in respiratory epithelium.

SARS-CoV-2, the culprit pathogen of COVID-19, elicits prominent immune responses and cytokine storms. Intracellular Cl- is a crucial regulator of host defense, whereas the role of Cl- signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains unclear. By using human respiratory epithelial cell lines, primary cultured human airway epithelial cells, and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge, we demonstrated that SARS-CoV-2 nucleocapsid (N) protein could interact with Smad3, which downregulated cystic fibrosis transmembrane conductance regulator (CFTR) expression via microRNA-145. The intracellular Cl- concentration ([Cl-]i) was raised, resulting in phosphorylation of serum glucocorticoid regulated kinase 1 (SGK1) and robust inflammatory responses. Inhibition or knockout of SGK1 abrogated the N protein-elicited airway inflammation. Moreover, N protein promoted a sustained elevation of [Cl-]i by depleting intracellular cAMP via upregulation of phosphodiesterase 4 (PDE4). Rolipram, a selective PDE4 inhibitor, countered airway inflammation by reducing [Cl-]i. Our findings suggested that Cl- acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 infection. Targeting the Cl- signaling pathway might be a novel therapeutic strategy for COVID-19.

Genetic characteristics of human coronavirus HKU1 in mainland China during 2018.

Human coronavirus HKU1 (HCoV-HKU1) is a pathogen that causes acute respiratory tract infections in children and circulates worldwide. To investigate the molecular characteristics and genetic diversity of HCoV-HKU1 in China, a molecular epidemiological analysis based on complete genome sequences was performed. A total of 68 endemic-HCoV-positive samples were identified from 1358 enrolled patients during 2018, including four HCoV-229E, nine HCoV-OC43, 24 HCoV-NL63, and 31 HCoV-HKU1. The detection rate of endemic HCoVs was 5.01% during 2018, while for HCoV-HKU1, it was 2.28%. Eight complete genomic sequences of HCoV-HKU1 were obtained and compared to 41 reference genome sequences corresponding to genotypes A, B, and C, obtained from the GenBank databank. Of the eight HKU1 sequences, four belonged to genotype A and four belonged to genotype B. No genotype C strains were detected in this study. For genotype A, 18 variations in the S protein with respect to the reference sequence were present in more than 5% of the sequences, whereas for genotype B, this number was 25. Most of the amino acid changes occurred in the S1 subunit. No amino acid substitutions were found in the sites that are essential for interaction with neutralizing antibodies, while a 510T amino acid insertion was found in almost one third of genotype B sequences. About 82-83, 85-89, and 88-89 predicted N-glycosylation sites and 7-13, 6-8, and 9 predicted O-glycosylation sites were found among the sequences of genotype A, B, and C, respectively. Six conserved O-glycosylation sites were present in all of the genotype A sequences. Only genotype A and B strains were detected after 2005. The S protein exhibited relatively high diversity, with most of the amino acid changes occurring in the S1 subunit.

Origin, virological features, immune evasion and intervention of SARS-CoV-2 Omicron sublineages.

Recently, a large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continuously emerged and posed a major threat to global public health. Among them, particularly, Omicron variant (B.1.1.529), first identified in November 2021, carried numerous mutations in its spike protein (S), and then quickly spread around the world. Currently, Omicron variant has expanded into more than one hundred sublineages, such as BA.1, BA.2, BA.2.12.1, BA.4 and BA.5, which have already become the globally dominant variants. Different from other variants of concern (VOCs) of SARS-CoV-2, the Omicron variant and its sublineages exhibit increased transmissibility and immune escape from neutralizing antibodies generated through previous infection or vaccination, and have caused numerous re-infections and breakthrough infections. In this prospective, we have focused on the origin, virological features, immune evasion and intervention of Omicron sublineages, which will benefit the development of next-generation vaccines and therapeutics, including pan-sarbecovirus and universal anti-CoV therapeutics, to combat currently circulating and future emerging Omicron sublineages as well as other SARS-CoV-2 variants.

Novel cleavage sites identified in SARS-CoV-2 spike protein reveal mechanism for cathepsin L-facilitated viral infection and treatment strategies.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important target for vaccine and drug development. However, the rapid emergence of variant strains with mutated S proteins has rendered many treatments ineffective. Cleavage of the S protein by host proteases is essential for viral infection. Here, we discovered that the S protein contains two previously unidentified Cathepsin L (CTSL) cleavage sites (CS-1 and CS-2). Both sites are highly conserved among all known SARS-CoV-2 variants. Our structural studies revealed that CTSL cleavage promoted S to adopt receptor-binding domain (RBD) "up" activated conformations, facilitating receptor-binding and membrane fusion. We confirmed that CTSL cleavage is essential during infection of all emerged SARS-CoV-2 variants (including the recently emerged Omicron variant) by pseudovirus (PsV) infection experiment. Furthermore, we found CTSL-specific inhibitors not only blocked infection of PsV/live virus in cells but also reduced live virus infection of ex vivo lung tissues of both human donors and human ACE2-transgenic mice. Finally, we showed that two CTSL-specific inhibitors exhibited excellent In vivo effects to prevent live virus infection in human ACE2-transgenic mice. Our work demonstrated that inhibition of CTSL cleavage of SARS-CoV-2 S protein is a promising approach for the development of future mutation-resistant therapy.

Spatial region-resolved proteome map reveals mechanism of COVID-19-associated heart injury.

Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.

Attitudes of Chinese immigrants in Canada towards the use of Traditional Chinese Medicine for prevention and management of COVID-19: a cross-sectional survey during the early stages of the pandemic

ObjectionThe objective of this study was to assess attitudes towards the use of Traditional Chinese Medicine (TCM) for COVID-19 among Chinese immigrants in Canada during the early stage of the COVID-19 pandemic.MethodsA cross-sectional study was conducted in April 2020 in Canada. Individuals aged 16 or older who were of Chinese origin and living in Canada at the time of the survey were invited to participate in an online survey. Descriptive and univariate statistics were performed to describe participant attitudes towards various preventive and treatment measures for COVID-19. Multiple logistic regression was used to identify independent associations with sociodemographic factors and attitudes.ResultsA total of 754 eligible respondents were included in the analysis. 65.8% of the participants were female, 77.2% had a university degree or higher and 28.6% were 55 years of age or older. Overall, 48.8% of the study participants believed that TCM was effective in preventing COVID-19% and 46.2% would use TCM if they had COVID-19-related symptoms. However, the corresponding numbers for western medicine were 20.8% and 39.9%, which were statistically lower (p<0.01). Older participants (55+vs <35, OR=3.55 (95% CI 2.05 to 6.14);35–54 vs <35, OR=1.98 (95% CI 1.27 to 3.08)) and those who were dissatisfied with their income (OR=2.47(95% CI 1.56 to 3.92)) were more likely to believe TCM was effective against COVID-19. Similarly, older participants (55+vs <35, OR=3.13 (95% CI 1.79 to 5.46);35–54 vs <35, OR=2.25 (95% CI 1.35 to 3.74)), females (OR=1.60 (95% CI 1.15 to 2.23)), and those born in mainland China (OR=10.49 (95% CI 2.32 to 47.39)) were more likely to use TCM if they had symptoms of COVID-19.ConclusionDespite the lack of scientific evidence to support its use, TCM was widely believed by Chinese immigrants in Canada to be an effective means of preventing COVID-19 and many also stated they would use it if they were experiencing symptoms of COVID-19.

Why customers have the intention to reuse food delivery apps: evidence from China

PurposeFood delivery apps (FDA) have been widely adopted by customers in online-to-offline (O2O) catering businesses. This study aims to explore the mechanism regarding the stickiness of FDA and indicates why customers have the intention to reuse them.Design/methodology/approachA research model was developed based on the e-commerce system successful model (ECSS model) and social influence theory. Using the data collected from 312 customers who have FDA usage experience via an online survey, the established model was empirically assessed by partial least squares based structural equation model.FindingsThe results show that factors including information quality, ease of use, convenience and various choices perceived by FDA users are significant antecedents of customer satisfaction and perceived value, which in turn positively influence customers' intention to reuse. Besides, informational social influence and normative social influence play important roles in directly or indirectly affecting customers' intention to reuse.Originality/valueThis study extends the e-commerce system success model and enriches the literature regarding stickiness of FDA. Besides, the understanding of social influence in FDA usage has been deepened by addressing its role in the ECSS model based on the features and contexts of such apps.

Relationship Between Myopia and Other Risk Factors With Anxiety and Depression Among Chinese University Freshmen During the COVID-19 Pandemic.

Purpose: To investigate the association of myopia and other risk factors with anxiety and depression among Chinese university freshmen during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This cross-sectional study was conducted at the Tianjin Medical University from October 2020 to December 2020. Ophthalmic examination of the eyes was performed by an experienced ophthalmologist. Detailed information on depression, anxiety, and other risk factors was collected via the Self-rating Anxiety Scale and Self-rating Depression Scale. Results: The overall prevalence of anxiety and depression in our study was 10.34 and 25.13%, respectively. The prevalence of myopia and high myopia as 92.02 and 26.7%, respectively. There were significant associations between anxiety and spectacle power [odds ratios (OR) = 0.89; 95% CI: 0.81-0.98, P = 0.019], sphere equivalent (OR = 0.89; 95% CI: 0.81- 0.98, P = 0.025), sleep time (OR = 0.53; 95% CI: 0.35-0.79, P = 0.002), and body mass index (OR = 0.93; 95% CI: 0.86-0.99, P = 0.047). In the multivariable linear regression models, spectacle power (ß = -0.43; 95% CI: -0.68 to -0.19, P = 0.001) and sphere equivalent (ß = -0.36; 95% CI: -0.60 to -0.11, P = 0.005) were negatively associated with anxiety scores, whereas axial length (ß = 0.54; 95% CI: 0.02-1.07, P = 0.044) was positively correlated with anxiety scores. Every 1 h decrease in sleep time was associated with a 0.12-point increase in depression score. Conclusion: Myopia was associated with anxiety and anxiety scores. The greater the degree of myopia, the higher the anxiety score. However, myopia was not found to be associated with depression. The results highlight the importance of providing psychological support to students with myopia during the COVID-19 pandemic.

Nanometer-resolution in situ structure of the SARS-CoV-2 postfusion spike protein.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates membrane fusion to allow entry of the viral genome into host cells. To understand its detailed entry mechanism and develop a specific entry inhibitor, in situ structural information on the SARS-CoV-2 spike protein in different states is urgent. Here, by using cryo-electron tomography, we observed both prefusion and postfusion spikes in ß-propiolactone-inactivated SARS-CoV-2 virions and solved the in situ structure of the postfusion spike at nanometer resolution. Compared to previous reports, the six-helix bundle fusion core, the glycosylation sites, and the location of the transmembrane domain were clearly resolved. We observed oligomerization patterns of the spikes on the viral membrane, likely suggesting a mechanism of fusion pore formation.