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1.
Preprint in English | bioRxiv | ID: ppbiorxiv-473930

ABSTRACT

Previous reports show that Ly49+CD8+ T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8+ T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent of the Ly49 family, in the blood and inflamed tissues of various autoimmune diseases. Moreover, KIR+CD8+ T cells can efficiently eliminate pathogenic gliadin-specific CD4+ T cells from Celiac disease (CeD) patients leukocytes in vitro. Furthermore, we observe elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 and influenza-infected patients, and this correlates with disease severity and vasculitis in COVID-19. Expanded KIR+CD8+ T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8+ T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells. One-Sentence SummaryHere we identified KIR+CD8+ T cells as a regulatory CD8+ T cell subset in humans that suppresses self-reactive or otherwise pathogenic CD4+ T cells.

2.
Administrative Sciences ; 11(4):144, 2021.
Article in English | MDPI | ID: covidwho-1554818

ABSTRACT

The COVID-19 pandemic had a devastating effect on the tourism and hospitality industries in Taiwan, causing some small companies to cease trading and large companies to place their employees on unpaid leave. Placing employees on unpaid leave may have negatively affected the intention of hospitality employees to remain in their jobs. This study examined whether employees’job insecurity and organizational identification affected their intention to stay in their job during the COVID-19 pandemic. Previously developed scales were adopted to develop items measuring job insecurity, organizational identification, and intention to stay in a job. Responses to 515 returned questionnaires were examined. The results revealed that job insecurity significantly affects organizational identification. Both job insecurity and organizational identification significantly affected intention to stay. Few studies have used path analyses to investigate the relationships among intention to stay, job insecurity, and organizational identification. The indirect effect of organizational identification was analyzed, and evidence supporting a total effect and total indirect effect was obtained. This implies that hospitality companies seeking to retain staff during crises should promote organizational identification among staff.

3.
EBioMedicine ; 74: 103722, 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1536517

ABSTRACT

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411 .

4.
Microbiol Spectr ; : e0088621, 2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1522922

ABSTRACT

The evaluation of humoral protective immunity against SARS-CoV-2 remains crucial in understanding both natural immunity and protective immunity conferred by the several vaccines implemented in the fight against COVID-19. The reference standard for the quantification of antibodies capable of neutralizing SARS-CoV-2 is the plaque-reduction neutralization test (PRNT). However, given that it is a laboratory-developed assay, validation is crucial in order to ensure sufficient specificity and intra- and interassay precision. In addition, a multitude of other serological assays have been developed, including enzyme-linked immunosorbent assay (ELISA), flow cytometry-based assays, luciferase-based lentiviral pseudotype assays, and commercially available human ACE2 receptor-blocking antibody tests, which offer practical advantages in the evaluation of the protective humoral response against SARS-CoV-2. In this study, we validated a SARS-CoV-2 PRNT to assess both 50% and 90% neutralization of SARS-CoV-2 according to guidelines outlined by the World Health Organization. Upon validation, the reference-standard PRNT demonstrated excellent specificity and both intra- and interassay precision. Using the validated assay as a reference standard, we characterized the neutralizing antibody response in specimens from patients with laboratory-confirmed COVID-19. Finally, we conducted a small-scale multilaboratory comparison of alternate SARS-CoV-2 PRNTs and surrogate neutralization tests. These assays demonstrated substantial to perfect interrater agreement with the reference-standard PRNT and offer useful alternatives to assess humoral immunity against SARS-CoV-2. IMPORTANCE SARS-CoV-2, the causal agent of COVID-19, has infected over 246 million people and led to over 5 million deaths as of October 2021. With the approval of several efficacious COVID-19 vaccines, methods to evaluate protective immune responses will be crucial for the understanding of long-term immunity in the rapidly growing vaccinated population. The PRNT, which quantifies SARS-CoV-2-neutralizing antibodies, is used widely as a reference standard to validate new platforms but has not undergone substantial validation to ensure excellent inter- and intraassay precision and specificity. Our work is significant, as it describes the thorough validation of a PRNT, which we then used as a reference standard for the comparison of several alternative serological methods to measure SARS-CoV-2-neutralizing antibodies. These assays demonstrated excellent agreement with the reference-standard PRNT and include high-throughput platforms, which can greatly enhance capacity to assess both natural and vaccine-induced protective immunity against SARS-CoV-2.

5.
Int J Environ Res Public Health ; 18(18)2021 09 14.
Article in English | MEDLINE | ID: covidwho-1409571

ABSTRACT

Disparities and their geospatial patterns exist in morbidity and mortality of COVID-19 patients. When it comes to the infection rate, there is a dearth of research with respect to the disparity structure, its geospatial characteristics, and the pre-infection determinants of risk (PIDRs). This work aimed to assess the temporal-geospatial associations between PIDRs and COVID-19 infection at the county level in South Carolina. We used the spatial error model (SEM), spatial lag model (SLM), and conditional autoregressive model (CAR) as global models and the geographically weighted regression model (GWR) as a local model. The data were retrieved from multiple sources including USAFacts, U.S. Census Bureau, and the Population Estimates Program. The percentage of males and the unemployed population were positively associated with geodistributions of COVID-19 infection (p values < 0.05) in global models throughout the time. The percentage of the white population and the obesity rate showed divergent spatial correlations at different times of the pandemic. GWR models fit better than global models, suggesting nonstationary correlations between a region and its neighbors. Characterized by temporal-geospatial patterns, disparities in COVID-19 infection rate and their PIDRs are different from the mortality and morbidity of COVID-19 patients. Our findings suggest the importance of prioritizing different populations and developing tailored interventions at different times of the pandemic.


Subject(s)
COVID-19 , Humans , Male , Pandemics , SARS-CoV-2 , South Carolina/epidemiology , Spatial Regression
7.
Applied Economics ; : 1-15, 2021.
Article in English | Taylor & Francis | ID: covidwho-1360226
9.
Ann Palliat Med ; 10(7): 7360-7369, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1344619

ABSTRACT

BACKGROUND: Rational use of antibiotics received great attention in China, therefore the multifaceted antimicrobial stewardship (MAMS) is urgently required in hospital management. We conducted this study to assess the impact of a MAMS programme on antimicrobial use in a tertiary teaching hospital in Shanghai. METHODS: This retrospective observational study was conducted at a tertiary teaching hospital in Shanghai. The MAMS programme involved multifaceted interventions consisting of a quality premium with financial incentives, antibiotic restriction, audit and feedback, and education. Data were extracted from the electronic medical records of inpatients to analyse monthly and annual antibiotic consumption and the percentage of antibiotic prescriptions during 2017-2020. Segmented regression analysis of the interrupted time series was used to contrast antimicrobial use during 2019-2020, with non-MAMS data from the 2017-2018 period as the historical control. RESULTS: With MAMS implementation, antibiotic consumption decreased from 63.3 (59.3, 67.2) defined daily doses (DDDs) per 100 patient-days (PD) to 43.3 (39.0, 49.8) DDDs/100 PD (P<0.001), and the percentage of antibiotic prescriptions decreased from 44.8% (44.1%, 45.4%) to 43.3% (42.2%, 44.3%) (P<0.001). Segmented regression models suggested a reduction in antibiotic consumption (coefficient = -12.537, P<0.001) and indicated a downward trend in the percentage of antibiotic prescriptions (coefficient =-0.165, P=0.049). Neither antibiotic consumption nor the percentage of antibiotic prescriptions was influenced by the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: This study suggests that MAMS plays an important role in reducing antibiotic use and is not affected by special circumstances such as the COVID-19 pandemic. This novel intervention, consisting of a quality premium and multidisciplinary cooperation, should be prioritized by policy and decision makers, where rational management of antimicrobial use is urgently needed.


Subject(s)
Anti-Infective Agents , Antimicrobial Stewardship , COVID-19 , Anti-Bacterial Agents/therapeutic use , China , Hospitals, Teaching , Humans , Pandemics , Regression Analysis , SARS-CoV-2
10.
Preprint in English | medRxiv | ID: ppmedrxiv-21259761

ABSTRACT

Emergence of SARS-CoV-2 with high transmission and immune evasion potential, the so-called Variants of Concern (VOC), is a major concern. We describe the early genomic epidemiology of SARS-CoV-2 recovered from vaccinated healthcare professionals (HCP). Our post-vaccination COVID-19 symptoms-based surveillance program among HCPs in a 17-hospital network, identified all vaccinated HCP who tested positive for COVID-19 after routine screening or after self-reporting. From 01/01/2021 to 04/30/2021, 23,687 HCP received either mRNA-1273 or BNT162b2 mRNA vaccine. All available post-vaccination SARS-CoV-2 samples and a random collection from non-vaccinated patients during the similar timeframe were subjected to VOC screening and whole genome sequencing (WGS). 62% (23,697/37,500) of HCPs received at least one vaccine dose, with 95% (22,458) fully vaccinated. We detected 138 (0.58%, 138/23,697) COVID-19 cases, 105 among partially vaccinated and 33 (0.15%, 33/22,458) among fully vaccinated. Five partially vaccinated required hospitalization, four with supplemental oxygen. VOC screening from 16 fully vaccinated HCPs identified 6 (38%) harboring N501Y and 1 (6%) with E484K polymorphisms; concurrent non-vaccinated samples was 37% (523/1404) and 20% (284/1394), respectively. There was an upward trend from January to April for E484K/Q (3% to 26%) and N501Y (1% to 49%). WGS analysis from vaccinated and non-vaccinated individuals indicated highly congruent phylogenies. We did not detect an increased frequency of any RBD/NTD polymorphism between groups (P>0.05). Our results support robust protection by vaccination, particularly among recipients of both doses. Despite VOCs accounting for over 40% of SARS-CoV-2 from fully vaccinated individuals, the genomic diversity appears to proportionally represent those among non-vaccinated populations. IMPORTANCEA number of highly effective vaccines have been developed and deployed to combat the COVID-19 pandemic. The emergence and epidemiological dominance of SARS-CoV-2 mutants, with high transmission potential and immune evasion properties, the so-called Variants of Concern (VOC), continues to be a major concern. Whether these VOCs alter the efficacy of the administered vaccines is of great concern, and a critical question to study. We describe the initial genomic epidemiology of SARS-CoV-2 recovered from vaccinated healthcare professionals and probe specifically for VOC enrichment. Our findings support the high-level of protection provided by full vaccination despite a steep increase in the prevalence of polymorphisms associated with increased transmission potential (N501Y) and immune evasion (E484K) in the non-vaccinated population. Thus, we do not find evidence of VOC enrichment among vaccinated groups. Overall, the genomic diversity of SARS-CoV-2 recovered post-vaccination appears to proportionally represent the observed viral diversity within the community.

11.
Epidemiology and Infection ; 149(e10), 2021.
Article in English | CAB Abstracts | ID: covidwho-1279751

ABSTRACT

This study aims to locate the knots of cumulative coronavirus disease 2019 (COVID-19) case number during the first-level response to public health emergency in the provinces of China except Hubei. The provinces were grouped into three regions, namely eastern, central and western provinces, and the trends between adjacent knots were compared among the three regions. COVID-19 case number, migration scale index, Baidu index, demographic, economic and public health resource data were collected from 22 Chinese provinces from 19 January 2020 to 12 March 2020. Spline regression was applied to the data of all included, eastern, central and western provinces. The research period was divided into three stages by two knots. The first stage (from 19 January to around 25 January) was similar among three regions. However, in the second stage, growth of COVID-19 case number was flatter and lasted longer in western provinces (from 25 January to 18 February) than in eastern and central provinces (from 26 February to around 11 February). In the third stage, the growth of COVID-19 case number slowed down in all the three regions. Included covariates were different among the three regions. Overall, spline regression with covariates showed the different change patterns in eastern, central and western provinces, which provided a better insight into regional characteristics of COVID-19 pandemic.

12.
J Biol Chem ; 297(1): 100821, 2021 07.
Article in English | MEDLINE | ID: covidwho-1240418

ABSTRACT

Viral proteins are known to be methylated by host protein arginine methyltransferases (PRMTs) necessary for the viral life cycle, but it remains unknown whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins are methylated. Herein, we show that PRMT1 methylates SARS-CoV-2 nucleocapsid (N) protein at residues R95 and R177 within RGG/RG motifs, preferred PRMT target sequences. We confirmed arginine methylation of N protein by immunoblotting viral proteins extracted from SARS-CoV-2 virions isolated from cell culture. Type I PRMT inhibitor (MS023) or substitution of R95 or R177 with lysine inhibited interaction of N protein with the 5'-UTR of SARS-CoV-2 genomic RNA, a property required for viral packaging. We also defined the N protein interactome in HEK293 cells, which identified PRMT1 and many of its RGG/RG substrates, including the known interacting protein G3BP1 as well as other components of stress granules (SGs), which are part of the host antiviral response. Methylation of R95 regulated the ability of N protein to suppress the formation of SGs, as R95K substitution or MS023 treatment blocked N-mediated suppression of SGs. Also, the coexpression of methylarginine reader Tudor domain-containing protein 3 quenched N protein-mediated suppression of SGs in a dose-dependent manner. Finally, pretreatment of VeroE6 cells with MS023 significantly reduced SARS-CoV-2 replication. Because type I PRMT inhibitors are already undergoing clinical trials for cancer treatment, inhibiting arginine methylation to target the later stages of the viral life cycle such as viral genome packaging and assembly of virions may represent an additional therapeutic application of these drugs.


Subject(s)
Arginine/metabolism , COVID-19/metabolism , COVID-19/virology , Nucleocapsid Proteins/chemistry , Nucleocapsid Proteins/metabolism , RNA, Viral/metabolism , SARS-CoV-2/physiology , Amino Acid Motifs , COVID-19/genetics , Cytoplasmic Granules/genetics , Cytoplasmic Granules/metabolism , HEK293 Cells , Humans , Methylation , Nucleocapsid Proteins/genetics , RNA Stability , RNA, Viral/chemistry , RNA, Viral/genetics , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Virus Replication
13.
Sustainability ; 13(9):4937, 2021.
Article in English | ProQuest Central | ID: covidwho-1238975

ABSTRACT

To discover how the lacquerware industry realizes its core competency, it is important to explore its upgrading strategies in the global value chains. The purpose of this study is to discuss the upgrading strategies applied during the lacquerware industry’s four economic stages and the approach to realize the industry’s sustainability. Results show that (1) OEM enterprises reach process upgrading with four strategies, ODM enterprises reach product upgrading with five strategies, OBM enterprises reach functional upgrading with four strategies, and OSM enterprises reach chain upgrading with two strategies;(2) the lacquerware industry‘s main elements in SSCM include the long-standing relations, reprocessing of defective products, employing the local community, and participation in regional and transregional development initiatives, wherein the design sector is the main link in the SSCM of the lacquerware. The result and implications provided by this study can serve as a reference for other lacquerware and local traditional handicraft industries that are seeking to upgrade and achieve sustainability during their economic development.

14.
Preprint in English | bioRxiv | ID: ppbiorxiv-444111

ABSTRACT

SARS-CoV-2 and its variants are raging worldwide. Unfortunately, the global vaccination is not efficient enough to attain a vaccine-based herd-immunity and yet no special and effective drug is developed to contain the spread of the disease. Previously we have identified CD147 as a novel receptor for SARS-CoV-2 infection. Here, we demonstrated that CD147 antibody effectively inhibits infection and cytokine storm caused by SARS-CoV-2 variants. In CD147KO VeroE6 cells, infections of SARS-CoV-2, its variants (B.1.1.7, B.1.351) and pseudovirus mutants (B.1.1.7, B.1.351, B.1.525, B.1.526 (S477N), B.1.526 (E484K), P.1, P.2, B.1.617.1, B.1.617.2) were decreased. Meanwhile, CD147 antibody effectively blocked the entry of variants and pseudomutants in VeroE6 cells, and inhibited the expression of cytokines. A model of SARS-CoV-2-infected hCD147 transgenic mice was constructed, which recapitulated the features of exudative diffuse alveolar damage and dynamic immune responses of COVID-19. CD147 antibody could effectively clear the virus and alveolar exudation, resolving the pneumonia. We found the elevated level of cyclophilin A (CyPA) in plasma of severe/critical cases, and identified CyPA as the most important proinflammatory intermediate causing cytokine storm. Mechanistically, spike protein of SARS-CoV-2 bound to CD147 and initiated the JAK-STAT pathway, which induced expression of CyPA. CyPA reciprocally bound to CD147, triggered MAPK pathway and consequently mediated the expression of cytokine and chemokine. In conclusion, CD147 is a critical target for SARS-CoV-2 variants and CD147 antibody is a promising drug to control the new wave of COVID-19 epidemic.

15.
Antiviral Res ; 190: 105078, 2021 06.
Article in English | MEDLINE | ID: covidwho-1198616

ABSTRACT

Antiviral therapeutics is one effective avenue to control and end this devastating COVID-19 pandemic. The viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 has been recognized as a valuable target of antivirals. However, the cell-free SARS-CoV-2 RdRp biochemical assay requires the conversion of nucleotide prodrugs into the active triphosphate forms, which regularly occurs in cells yet is a complicated multiple-step chemical process in vitro, and thus hinders the utility of this cell-free assay in the rapid discovery of RdRp inhibitors. In addition, SARS-CoV-2 exoribonuclease provides the proof-reading capacity to viral RdRp, thus creates relatively high resistance threshold of viral RdRp to nucleotide analog inhibitors, which must be examined and evaluated in the development of this class of antivirals. Here, we report a cell-based assay to evaluate the efficacy of nucleotide analog compounds against SARS-CoV-2 RdRp and assess their tolerance to viral exoribonuclease-mediated proof-reading. By testing seven commonly used nucleotide analog viral polymerase inhibitors, Remdesivir, Molnupiravir, Ribavirin, Favipiravir, Penciclovir, Entecavir and Tenofovir, we found that both Molnupiravir and Remdesivir showed the strong inhibition of SARS-CoV-2 RdRp, with EC50 value of 0.22 µM and 0.67 µM, respectively. Moreover, our results suggested that exoribonuclease nsp14 increases resistance of SARS-CoV-2 RdRp to nucleotide analog inhibitors. We also determined that Remdesivir presented the highest resistance to viral exoribonuclease activity in cells. Therefore, we have developed a cell-based SARS-CoV-2 RdRp assay which can be deployed to discover SARS-CoV-2 RdRp inhibitors that are urgently needed to treat COVID-19 patients.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Discovery , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , A549 Cells , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/pharmacology , COVID-19/virology , Cell Survival/drug effects , Exoribonucleases/antagonists & inhibitors , HEK293 Cells , High-Throughput Screening Assays , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , Viral Nonstructural Proteins/antagonists & inhibitors
16.
Preprint in English | medRxiv | ID: ppmedrxiv-21254791

ABSTRACT

SARS-CoV-2 Variants of Concerns (VOC), e.g., B.1.351 (20H/501Y.V2) and P1 (20J/501Y.V3), harboring N-terminal domain (NTD) or the receptor-binding domain (RBD) (e.g., E484K) mutations, exhibit reduced in vitro susceptibility to convalescent serum, commercial antibody cocktails, and vaccine neutralization, and have been associated with reinfection. The accumulation of these mutations could be the consequence of intra-host viral evolution due to prolonged infection in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on tacrolimus, steroids and convalescent plasma therapy, and identify the emergence of multiple NTD and RBD mutations associated with reduced antibody neutralization as early as three weeks after infection. SARS-CoV-2 genomes from the first swab (Day 0) and three tracheal aspirates (Day 7, 21 and 27) were compared at the sequence level. We identified five different S protein mutations at the NTD or RBD regions from the second tracheal aspirate sample (21 Day). The S:Q493R substitution and S:243-244LA deletion had [~]70% frequency, while ORF1a:A138T, S:141-144LGVY deletion, S:E484K and S:Q493K substitutions demonstrated [~]30%, [~]30%, [~]20% and [~]10% mutation frequency, respectively. However, the third tracheal aspirate sample collected one week later (Day 27) was predominated by the haplotype of ORF1a:A138T, S:141-144LGVY deletion and S:E484K (> 95% mutation frequency). Notably, S protein deletions (141-144LGVY and 243-244LA deletions in NTD region) and substitutions (Q493K/R and E484K in the RBD region) previously showed reduced susceptibly to monoclonal antibody or convalescent plasma. The observation supports the hypothesis that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune-escape mutants. Competing Interest StatementThe authors have declared no competing interest. Funding StatementThe study was in part supported by Center for Discovery and Innovation and Hackensack Meridian Health Foundation.

17.
Preprint in English | medRxiv | ID: ppmedrxiv-21253712

ABSTRACT

Spike protein mutations E484K and N501Y carried by SARS-CoV-2 variants have been associated with concerning changes of the virus, including resistance to neutralizing antibodies and increased transmissibility. While the concerning variants are fast spreading in various geographical areas, identification and monitoring of these variants is lagging far behind, due in large part to the slow speed and insufficient capacity of viral sequencing. In response to the unmet need for a fast and efficient screening tool, we developed a single-tube duplex molecular assay for rapid and simultaneous identification of E484K and N501Y mutations from nasopharyngeal swab (NS) samples within 2.5 h from sample preparation to report. Using this tool, we screened a total of 435 clinical NS samples collected from COVID patients at 8 hospitals within the Hackensack Meridian Health network in New Jersey. While B.1.351 and P.1 variants were absent from the current study, our data revealed a dramatic increase in the frequency of E484K over time, underscoring the need for continuous epidemiological monitoring.

18.
Acta Pharm Sin B ; 11(6): 1555-1567, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1082559

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC50) value of 0.13 µmol/L. Computation modeling predicts that RAI-S-37 lands at the palm domain of RdRp and prevents conformational changes required for nucleotide incorporation by RdRp. In addition, combination of RAI-S-37 with remdesivir exhibits additive activity against anti-SARS-CoV-2 RdRp. Together with the current data available on the safety and pharmacokinetics of corilagin as a medicinal herbal agent, these results demonstrate the potential of being developed into one of the much-needed SARS-CoV-2 therapeutics.

19.
Journal of Membrane Science ; : 119123, 2021.
Article in English | ScienceDirect | ID: covidwho-1071775

ABSTRACT

Compared with traditional methods for elaborately tailoring the active layer of thin-film composite (TFC) membranes, this study focused on building novel substrates for potential applications in developing organic solvent nanofiltration (OSN) membranes. One kind of “three-parts” hierarchically structured interface with nanospheres and macro surface pores was successfully prepared via Michael addition and Schiff's base (M&S) reactions between N-(2-aminoethyl)-3-aminopropyl triethoxysilane (NAE-A) and glycerite (a natural polyphenol) in the aramid substrate. The thickness was reduced to sub10 μm with the aid of the high-speed spin coating process coupling nonsolvent-induced phase separation (HSSC-co-NIPS) method. The composition characterization results demonstrated the introduction of glycerite, and the reactions occurred in/on the substrate. Scanning electron microscopy (SEM) images clearly showed that the sub10 μm substrate contained a “three-level” hierarchically structured interface that included: (1) a “stalk-like” structure;(2) glycerite-NAE-A silane (GNAS) nanospheres;and (3) the substrate surface. These phenomena also resulted in better surface hydrophilicity. All types of organic solvents, including harsh solvents, such as tetrahydrofuran (THF) and N,N-dimethylformamide (DMF), had stable permeability within the substrate, as did apolar n-hexane and isopar™ G. Therefore, the as-prepared TFC OSN membrane, which had an extremely short polymerization time, retained broad-spectrum solvent stability and had the highest solvent permeance in acetonitrile (24.5 ± 0.4 L m−2 h−1·bar−1). In addition, the resultant TFC membrane almost completely rejected the popular macrolide antibiotic azithromycin (AZM, 748.98 g mol−1) in ethanol, which is used to treat COVID-19.

20.
Epidemiol Infect ; 149: e10, 2021 01 05.
Article in English | MEDLINE | ID: covidwho-1065748

ABSTRACT

This study aims to locate the knots of cumulative coronavirus disease 2019 (COVID-19) case number during the first-level response to public health emergency in the provinces of China except Hubei. The provinces were grouped into three regions, namely eastern, central and western provinces, and the trends between adjacent knots were compared among the three regions. COVID-19 case number, migration scale index, Baidu index, demographic, economic and public health resource data were collected from 22 Chinese provinces from 19 January 2020 to 12 March 2020. Spline regression was applied to the data of all included, eastern, central and western provinces. The research period was divided into three stages by two knots. The first stage (from 19 January to around 25 January) was similar among three regions. However, in the second stage, growth of COVID-19 case number was flatter and lasted longer in western provinces (from 25 January to 18 February) than in eastern and central provinces (from 26 February to around 11 February). In the third stage, the growth of COVID-19 case number slowed down in all the three regions. Included covariates were different among the three regions. Overall, spline regression with covariates showed the different change patterns in eastern, central and western provinces, which provided a better insight into regional characteristics of COVID-19 pandemic.


Subject(s)
COVID-19/epidemiology , SARS-CoV-2 , China/epidemiology , Emergencies , Humans , Public Health , Regression Analysis
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