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1.
Pakistan Journal of Zoology ; 54(4):1747, 2022.
Article in English | ProQuest Central | ID: covidwho-1837983

ABSTRACT

In this paper, an epidemiological study was performed by focusing on all confirmed patients with COVID-19 in Xuzhou, a prefecture-level city, and a transportation hub with 10.44 million population in the east region of China. The median age of the patients is 42-year-old and 45.57% are male;25 cases (31.65%) are imported. 23 cases (29.11%) were confirmed between January 26 to 31, 2020 while 56 cases (70.89%) were from February 1 to 16, 2020. Among the ten administrative divisions of Xuzhou city, Suining county (n=31) and Pizhou City (n=15) have the most cases while Tongshan district has none. A representative familial cluster with 6 cases was analyzed in detail in order to get a better understanding of the transmission routes of the virus. Furthermore, we performed a retrospective, single-centre study of 41 COVID-19 patients at Xuzhou Infectious Diseases Hospital in terms of clinical findings, which provided an insightful understanding of the disease.

2.
Advanced Theory and Simulations ; 5(4):2270010, 2022.
Article in English | Wiley | ID: covidwho-1782559

ABSTRACT

Impacts of Export Restrictions on the Global Personal Protective Equipment Trade Network During COVID-19 In article number 2100352, Ye, Zhang and co-workers investigate the effect of personal protective equipment (PPE) shortages on COVID-19 contagion patterns. Integrating a metapopulation model and a threshold model, it is found that export restrictions on PPE cause shortage contagion on the global PPE trade network to transmit even faster than the disease contagion on global mobility network.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324610

ABSTRACT

Motivated by the importance of individual differences in risk perception and behavior change in people's responses to infectious disease outbreaks (particularly the ongoing COVID-19 pandemic), we propose a heterogeneous Disease-Behavior-Information (hDBI) transmission model, in which people's risk of getting infected is influenced by information diffusion, behavior change, and disease transmission. We use both a mean-field approximation and Monte Carlo simulations to analyze the dynamics of the model. Information diffusion influences behavior change by allowing people to be aware of the disease and adopt self-protection, and subsequently affects disease transmission by changing the actual infection rate. Results show that (a) awareness plays a central role in epidemic prevention;(b) a reasonable fraction of "over-reacting" nodes are needed in epidemic prevention;(c) R0 has different effects on epidemic outbreak for cases with and without asymptomatic infection;(d) social influence on behavior change can remarkably decrease the epidemic outbreak size. This research indicates that the media and opinion leaders should not understate the transmissibility and severity of diseases to ensure that people could become aware of the disease and adopt self-protection to protect themselves and the whole population.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324609

ABSTRACT

The COVID-19 pandemic has caused a dramatic surge in demand for personal protective equipment (PPE) worldwide. Many countries have imposed export restrictions on PPE to ensure the sufficient domestic supply. The surging demand and export restrictions cause shortage contagions on the global PPE trade network. Here, we develop an integrated network model, which integrates a metapopulation model and a threshold model, to investigate the shortage contagion patterns. The metapopulation model captures disease contagion across countries. The threshold model captures the shortage contagion on the global PPE trade network. Results show that, the shortage contagion patterns are mainly decided by top exporters. Export restrictions exacerbate the shortages of PPE and cause the shortage contagion to transmit even faster than the disease contagion. Besides, export restrictions lead to ineffective and inefficient allocation of PPE around the world, which has no benefits for the world to fight against the pandemic.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322991

ABSTRACT

Background: To compare clinical features between moderate and severe cases with COVID-19, and screen factors associated with disease severity. Methods: : Demographic and clinical data were compared between moderate and severe cases. Logistic regression was performed for prognostic factors. Results: : 163 patients (median age 65.0 (56.8-71.0) years, 78 (47.9%) females) were enrolled, including 87 (53.4%) severe and 76 (46.6%) moderate cases. 79 (90.8%) severe and 59 (77.6%) moderate cases had comorbidities, with hypertension and diabetes commonly presented. The most common symptoms were fever. Severe cases had higher lactate dehydrogenase (LDH), inflammatory cytokines and lymphopenia, eosinopenia on admission, and lower eosinophil and higher neutrophil counts from admission to day 13 and 19. Multivariable regression showed that neutrophilia, eosinopenia, high LDH and D-dimer were associated with severe COVID-19. In receiver operating characteristic curve analysis, LDH, eosinophil and neutrophil + eosinophil + LDH + D-dimer combination, with area under curve of 0.86, 0.76 and 0.93, predicted severe illness with high sensitivity (82.8%, 83.3%, 88.0%) and specificity (68.4%, 84.2%, 81.3%). Conclusions: : Eosinopenia, higher LDH and neutrophil + eosinophil + LDH + D-dimer combination on admission were powerful indicators of severe COVID-19. Dynamic changes of neutrophils and eosinophils may be used to evaluate disease progression.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315626

ABSTRACT

The therapeutic effect of tocilizumab remains controversial. We aimed to evaluate whether tocilizumab might be beneficial in COVID-19 patients. We searched PubMed, Embase and Cochrane library from inception to June 23, 2020. Summary estimates of overall response rate (ORR) and all-cause death rate in all patients were analyzed. This study was registered with PROSPERO (CRD42020191313). We included data from 28 articles including 991 COVID-19 patients who underwent tocilizumab administration. The pooled ORR was 72% (95% CI, 66-79%) and pooled all-cause death rate was 16% (95% CI, 11-22%). The optimal timing of administration was the 7.15 day from the symptom onset and with the lowest death rate of 13.11%. 562 patients were defined as with severe infection, and the pooled ORR was 78% (95% CI, 70-85%). The pooled ORR of 56 organ transplantation recipients was 53% (95% CI, 26-78%), which was lower than non-transplant patients [75% (95% CI, 69-81%)]. Nearly all studies confirmed the safety of tocilizumab administration. Tocilizumab improves the clinical outcome of COVID-19 patients, especially in severe cases, and the optimal timing of administration may provide the guidance for management. However, tocilizumab may be used with caution in solid transplant recipients for the suboptimal efficacy.

7.
J Pharm Biomed Anal ; 209: 114538, 2022 Feb 05.
Article in English | MEDLINE | ID: covidwho-1670797

ABSTRACT

The 3C-like protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to the virus life cycle and is supposed to be a potential target for the treatment of coronaviral infection. Traditional Chinese medicines (TCMs) have played an impressive role in the treatment of COVID-19 in China. The effectiveness of TCM formulations prompts scientists to take continuous effort on searching for bioactive small molecules from the ancient resources. Herein, we developed a native mass spectrometry-based affinity-selection method for rapid screening of active small molecules from crude herbal extracts applied for COVID-19 therapy. Six common herbs named Lonicera japonica, Scutellaria baicalensis, Forsythia suspensa, Glycyrrhiza uralensis, Cirsium japonicum, and Andrographis paniculata were investigated. After preliminary separation of the crude extracts, the fractions were incubated with 3CLpro. A native MS-based affinity screening assay was then conducted to search for the protein-ligand complexes. A UHPLC-Q/TOF-MS with UNIFI data acquisition and data processing software was applied to identify the hit compounds. Standard compounds were used to verify the outcomes. Among the 16 hits, three flavonoids, baicalein, scutellarein and ganhuangenin, were identified as potential noncovalent inhibitors against 3CLpro with IC50 values of 0.94, 3.02, and 0.84 µM, respectively. Their binding affinities were further characterized by native MS, with Kd values being 1.43, 3.85, and 1.09 µM, respectively. Overall, we established an efficient native MS-based strategy for discovering 3CLpro ligands from crude mixtures, which supplies a potential strategy of small molecule lead discovery from TCMs.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Peptide Hydrolases , Protease Inhibitors/pharmacology
8.
Nat Hum Behav ; 6(2): 207-216, 2022 02.
Article in English | MEDLINE | ID: covidwho-1661962

ABSTRACT

Despite broad agreement on the negative consequences of vaccine inequity, the distribution of COVID-19 vaccines is imbalanced. Access to vaccines in high-income countries (HICs) is far greater than in low- and middle-income countries (LMICs). As a result, there continue to be high rates of COVID-19 infections and deaths in LMICs. In addition, recent mutant COVID-19 outbreaks may counteract advances in epidemic control and economic recovery in HICs. To explore the consequences of vaccine (in)equity in the face of evolving COVID-19 strains, we examine vaccine allocation strategies using a multistrain metapopulation model. Our results show that vaccine inequity provides only limited and short-term benefits to HICs. Sharper disparities in vaccine allocation between HICs and LMICs lead to earlier and larger outbreaks of new waves. Equitable vaccine allocation strategies, in contrast, substantially curb the spread of new strains. For HICs, making immediate and generous vaccine donations to LMICs is a practical pathway to protect everyone.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Healthcare Disparities , Developing Countries , Humans
9.
Adv Theory Simul ; 5(4): 2100352, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1557820

ABSTRACT

The COVID-19 pandemic has caused a dramatic surge in demand for personal protective equipment (PPE) worldwide. Many countries have imposed export restrictions on PPE to ensure the sufficient domestic supply. The surging demand and export restrictions cause shortage contagions on the global PPE trade network. Here, an integrated network model is developed, which integrates a metapopulation model and a threshold model, to investigate the shortage contagion patterns. The metapopulation model captures disease contagion across countries. The threshold model captures the shortage contagion on the global PPE trade network. Due to the Pareto distribution in global exports, the shortage contagion pattern is mainly determined by the export restriction policies of the top exporters. Export restrictions exacerbate the shortages of PPE and cause the shortage contagion to transmit even faster than the disease contagion. To some extent, export restrictions can provide benefits for self-sufficient countries, at the sacrifice of immediate economic shocks at not-self-sufficient countries. With export restrictions, a large amount of PPE is hoarded instead of being distributed to where it is most needed, particularly at the early stage. Cooperation between countries plays an essential role in preventing global shortages of PPE regardless of the production level. Except for promoting global cooperation, governments and international organizations should take actions to reduce supply chain barriers and work together to increase global PPE production.

10.
Anal Chem ; 93(46): 15288-15294, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1500403

ABSTRACT

Herein, a pipette-tip-enabled digital nucleic acid analyzer for high-performance COVID-19 testing is demonstrated. This is achieved by digital loop-mediated isothermal amplification (digital LAMP or dLAMP) using common laboratory equipment and materials. It is shown that simply fixing a glass capillary inside conventional pipette tips enables the generation of monodisperse, water-in-oil microdroplets with benchtop centrifugation. It is shown that using LAMP, the ORF1a/b gene, a standard test region for COVID-19 screening, can be amplified without a thermal cycler. The amplification allows counting of fluorescent microdroplets so that Poisson analysis can be performed to allow quantification with a limit of detection that is 1 order of magnitude better than those of nondigital techniques and comparable to those of commercial dLAMP platforms. It is envisioned that this work will inspire studies on ultrasensitive digital nucleic acid analyzers demanding both sensitivity and accessibility, which is pivotal to their large-scale applications.


Subject(s)
COVID-19 Testing/methods , COVID-19 , Nucleic Acid Amplification Techniques , COVID-19/diagnosis , Humans , Molecular Diagnostic Techniques
11.
Front Bioeng Biotechnol ; 9: 735711, 2021.
Article in English | MEDLINE | ID: covidwho-1477801

ABSTRACT

In this work, it is shown that surface-enhanced Raman scattering (SERS) measurements can be performed using liquid platforms to perform bioanalysis at sub-pM concentrations. Using magnetic enrichment with gold-coated magnetic nanoparticles, the high sensitivity was verified with nucleic acid and protein targets. The former was performed with a DNA fragment associated with the bacteria Staphylococcus aureus, and the latter using IgG antibody, a biomarker for COVID-19 screening. It is anticipated that this work will inspire studies on ultrasensitive SERS analyzers suitable for large-scale applications, which is particularly important for in vitro diagnostics and environmental studies.

13.
Cell Res ; 31(10): 1047-1060, 2021 10.
Article in English | MEDLINE | ID: covidwho-1380899

ABSTRACT

The outbreak of SARS-CoV-2 (SARS2) has caused a global COVID-19 pandemic. The spike protein of SARS2 (SARS2-S) recognizes host receptors, including ACE2, to initiate viral entry in a complex biomechanical environment. Here, we reveal that tensile force, generated by bending of the host cell membrane, strengthens spike recognition of ACE2 and accelerates the detachment of spike's S1 subunit from the S2 subunit to rapidly prime the viral fusion machinery. Mechanistically, such mechano-activation is fulfilled by force-induced opening and rotation of spike's receptor-binding domain to prolong the bond lifetime of spike/ACE2 binding, up to 4 times longer than that of SARS-S binding with ACE2 under 10 pN force application, and subsequently by force-accelerated S1/S2 detachment which is up to ~103 times faster than that in the no-force condition. Interestingly, the SARS2-S D614G mutant, a more infectious variant, shows 3-time stronger force-dependent ACE2 binding and 35-time faster force-induced S1/S2 detachment. We also reveal that an anti-S1/S2 non-RBD-blocking antibody that was derived from convalescent COVID-19 patients with potent neutralizing capability can reduce S1/S2 detachment by 3 × 106 times under force. Our study sheds light on the mechano-chemistry of spike activation and on developing a non-RBD-blocking but S1/S2-locking therapeutic strategy to prevent SARS2 invasion.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Tensile Strength , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Neutralizing/immunology , Binding Sites , COVID-19/therapy , COVID-19/virology , Humans , Hydrogen-Ion Concentration , Immunization, Passive , Molecular Dynamics Simulation , Protein Binding , Protein Domains/immunology , Protein Subunits/chemistry , Protein Subunits/immunology , Protein Subunits/metabolism , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Virus Internalization
14.
Acta Pharmacol Sin ; 43(4): 788-796, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1343437

ABSTRACT

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , COVID-19/drug therapy , Humans , Protein Binding , SARS-CoV-2
15.
ACS Pharmacol Transl Sci ; 4(3): 1096-1110, 2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1313542

ABSTRACT

Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We here report the results of a repurposing program involving 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and small molecules regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro and have identified 62 additional compounds with IC50 values below 1 µM and profiled their selectivity toward chymotrypsin and 3CL-Pro from the Middle East respiratory syndrome virus. A subset of eight inhibitors showed anticytopathic effect in a Vero-E6 cell line, and the compounds thioguanosine and MG-132 were analyzed for their predicted binding characteristics to SARS-CoV-2 3CL-Pro. The X-ray crystal structure of the complex of myricetin and SARS-Cov-2 3CL-Pro was solved at a resolution of 1.77 Å, showing that myricetin is covalently bound to the catalytic Cys145 and therefore inhibiting its enzymatic activity.

16.
Nat Commun ; 12(1): 3623, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1270656

ABSTRACT

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) urgently needs an effective cure. 3CL protease (3CLpro) is a highly conserved cysteine proteinase that is indispensable for coronavirus replication, providing an attractive target for developing broad-spectrum antiviral drugs. Here we describe the discovery of myricetin, a flavonoid found in many food sources, as a non-peptidomimetic and covalent inhibitor of the SARS-CoV-2 3CLpro. Crystal structures of the protease bound with myricetin and its derivatives unexpectedly revealed that the pyrogallol group worked as an electrophile to covalently modify the catalytic cysteine. Kinetic and selectivity characterization together with theoretical calculations comprehensively illustrated the covalent binding mechanism of myricetin with the protease and demonstrated that the pyrogallol can serve as an electrophile warhead. Structure-based optimization of myricetin led to the discovery of derivatives with good antiviral activity and the potential of oral administration. These results provide detailed mechanistic insights into the covalent mode of action by pyrogallol-containing natural products and a template for design of non-peptidomimetic covalent inhibitors against 3CLpros, highlighting the potential of pyrogallol as an alternative warhead in design of targeted covalent ligands.


Subject(s)
Coronavirus 3C Proteases/drug effects , Pyrogallol/chemistry , Pyrogallol/isolation & purification , Pyrogallol/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Coronavirus Papain-Like Proteases , Drug Design , Flavonoids , HEK293 Cells , Humans , Kinetics , Ligands , Molecular Dynamics Simulation , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Viral Nonstructural Proteins/chemistry
17.
Urban For Urban Green ; 62: 127126, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1182722

ABSTRACT

COVID-19 case numbers in 161 sub-districts of Wuhan were investigated based on landscape epidemiology, and their landscape metrics were calculated based on land use/land cover (LULC). Initially, a mediation model verified a partially mediated population role in the relationship between landscape pattern and infection number. Adjusted incidence rate (AIR) and community safety index (CSI), two indicators for infection risk in sub-districts, were 25.82∼63.56 ‱ and 3.00∼15.87 respectively, and central urban sub-districts were at higher infection risk. Geographically weighted regression (GWR) performed better than OLS regression with AICc differences of 7.951∼181.261. The adjusted R2 in GWR models of class-level index and infection risk were 0.697 to 0.817, while for the landscape-level index they were 0.668 to 0.835. Secondly, 16 key landscape metrics were identified based on GWR, and then a prediction model for infection risk in sub-districts and communities was developed. Using principal component analysis (PCA), development intensity, landscape level, and urban blue-green space were considered to be principal components affecting disease infection risk, explaining 73.1 % of the total variance. Cropland (PLAND and LSI), urban land (NP, LPI, and LSI) and unused land (NP) represent development intensity, greatly affecting infection risk in urban areas. Landscape level CONTAG, DIVISION, SHDI, and SHEI represent mobility and connectivity, having a profound impact on infection risk in both urban and suburban areas. Water (PLAND, NP, LPI, and LSI) and woodland (NP, and LSI) represent urban blue-green spaces, and were particularly important for infection risk in suburban areas. Based on urban landscape pattern, we proposed a framework to understand and evaluate infection risk. These findings provide a basis for risk evaluation and policy-making of urban infectious disease, which is significant for community management and urban planning for infectious disease worldwide.

18.
Preprint in English | bioRxiv | ID: ppbiorxiv-424442

ABSTRACT

Pseudoviruses are useful surrogates for highly pathogenic viruses because of their safety, genetic stability, and scalability for screening assays. Many different pseudovirus platforms exist, each with different advantages and limitations. Here we report our efforts to optimize and characterize an HIV-based lentiviral pseudovirus assay for screening neutralizing antibodies for SARS-CoV-2 using a stable 293T cell line expressing human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We assessed different target cells, established conditions that generate readouts over at least a two-log range, and confirmed consistent neutralization titers over a range of pseudovirus input. Using reference sera and plasma panels, we evaluated assay precision and showed that our neutralization titers correlate well with results reported in other assays. Overall, our lentiviral assay is relatively simple, scalable, and suitable for a variety of SARS-CoV-2 entry and neutralization screening assays.

19.
Phys Rev E ; 102(4-1): 042314, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-920840

ABSTRACT

Motivated by the importance of individual differences in risk perception and behavior change in people's responses to infectious disease outbreaks (particularly the ongoing COVID-19 pandemic), we propose a heterogeneous disease-behavior-information transmission model, in which people's risk of getting infected is influenced by information diffusion, behavior change, and disease transmission. We use both a mean-field approximation and Monte Carlo simulations to analyze the dynamics of the model. Information diffusion influences behavior change by allowing people to be aware of the disease and adopt self-protection and subsequently affects disease transmission by changing the actual infection rate. Results show that (a) awareness plays a central role in epidemic prevention, (b) a reasonable fraction of overreacting nodes are needed in epidemic prevention (c) the basic reproduction number R_{0} has different effects on epidemic outbreak for cases with and without asymptomatic infection, and (d) social influence on behavior change can remarkably decrease the epidemic outbreak size. This research indicates that the media and opinion leaders should not understate the transmissibility and severity of diseases to ensure that people become aware of the disease and adopt self-protection to protect themselves and the whole population.


Subject(s)
Behavior , Disease Transmission, Infectious , Models, Theoretical , COVID-19/epidemiology , COVID-19/transmission , Diffusion , Humans , Monte Carlo Method , Pandemics , Perception , Risk Assessment
20.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-802

ABSTRACT

Background: Early invasive ventilation can effectively improve oxygenation and delay the disease progression of critically ill patients with coronavirus disease

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