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1.
Biosensors and Bioelectronics ; : 114293, 2022.
Article in English | ScienceDirect | ID: covidwho-1797125

ABSTRACT

In the wake of a pandemic, the development of rapid, simple, and accurate molecular diagnostic tests can significantly aid in reducing the spread of infections. By combining particle imaging with molecular assays, a quick and highly sensitive biosensor can readily identify a pathogen at low concentrations. Here, we implement functionalized particle-enabled rotational diffusometry in combination with loop-mediated isothermal amplification for the rapid detection of the SARS-CoV-2 nsp2 gene in the recombinant plasmid as a proof of concept for COVID-19 diagnostics. By analyzing the images of blinking signals generated by these modified particles, the change in micro-level viscosity due to nucleic acid amplification was measured. The high sensitivity of rotational diffusometry enabled facile detection within 10 min, with a limit of detection of 70 ag/μL and a sample volume of 2 μL. Tenfold higher detection sensitivity was observed for rotational diffusometry in comparison with real-time PCR. In addition, the system stability and the effect of temperature on rotational diffusometric measurements were studied and reported. These results demonstrated the utility of a rotational diffusometric platform for the rapid and sensitive detection of SARS-CoV-2 cDNA fragments.

2.
J Virol ; : e0201321, 2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1779314

ABSTRACT

The high mutation rate of COVID-19 and the prevalence of multiple variants strongly support the need for pharmacological options to complement vaccine strategies. One region that appears highly conserved among different genera of coronaviruses is the substrate-binding site of the main protease (Mpro or 3CLpro), making it an attractive target for the development of broad-spectrum drugs for multiple coronaviruses. PF-07321332, developed by Pfizer, is the first orally administered inhibitor targeting the main protease of SARS-CoV-2, which also has shown potency against other coronaviruses. Here, we report three crystal structures of the main protease of SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome (MERS)-CoV bound to the inhibitor PF-07321332. The structures reveal a ligand-binding site that is conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV, providing insights into the mechanism of inhibition of viral replication. The long and narrow cavity in the cleft between domains I and II of the main protease harbors multiple inhibitor-binding sites, where PF-07321332 occupies subsites S1, S2, and S4 and appears more restricted than other inhibitors. A detailed analysis of these structures illuminated key structural determinants essential for inhibition and elucidated the binding mode of action of the main proteases from different coronaviruses. Given the importance of the main protease for the treatment of SARS-CoV-2 infection, insights derived from this study should accelerate the design of safer and more effective antivirals. IMPORTANCE The current pandemic of multiple variants has created an urgent need for effective inhibitors of SARS-CoV-2 to complement vaccine strategies. PF-07321332, developed by Pfizer, is the first orally administered coronavirus-specific main protease inhibitor approved by the FDA. We solved the crystal structures of the main protease of SARS-CoV-2, SARS-CoV, and MERS-CoV that bound to the PF-07321332, suggesting PF-07321332 is a broad-spectrum inhibitor for coronaviruses. Structures of the main protease inhibitor complexes present an opportunity to discover safer and more effective inhibitors for COVID-19.

4.
Clin Med Insights Arthritis Musculoskelet Disord ; 15: 11795441221081061, 2022.
Article in English | MEDLINE | ID: covidwho-1759636

ABSTRACT

Under the ongoing COVID-19 pandemic, vaccines have become the crucial players to reduce the spread of the infection. Among them, the ChAdOx1 nCoV-19 vaccine is an adenoviral vector vaccine with an overall efficacy of 70.4% in protection. The engineered adenovirus contains the SARS-CoV-2 spike protein gene and pushes its DNA into the vaccinated cell's nucleus and subsequently, the spike protein can be made. During vaccination, the genome transition of adenovirus is influenced by the architecture and dynamics of the microtubule. Colchicine can alter microtubule dynamics by suppressing microtubule dynamics at lower concentrations and inducing depolymerization of microtubules at higher concentrations. Accordingly, the delivery of the genome to the vaccinated cell's nucleus by the adenoviral vector could be hindered under the presence of colchicine. Nevertheless, colchicine is a common medication for gout therapy worldwide, and though not recommended by guidelines, colchicine has even been taken into consideration as a possible therapeutic option for COVID-19 infection. Given the above reasons and the worldwide use of colchicine, the impact of colchicine on the efficacy of the COVID-19 vaccine via adenoviral vector should be viewed cautiously.

5.
J Pers Med ; 12(2)2022 Feb 04.
Article in English | MEDLINE | ID: covidwho-1715470

ABSTRACT

(1) Background: Virtual reality (VR) technology is a widely used training tool in medical education. The present study aimed to evaluate the effectiveness of VR training of oral hygiene students on providing oral healthcare to disabled elderly persons. (2) Methods: A randomized controlled trial was conducted. In 2021, oral hygiene students were randomly assigned to a VR experimental group (EG; n = 11) and a control group (CG; n = 12). The EG received two-hour, thrice-repeated VR-based training interventions at 2-week, 4-week, and 6-week follow-ups. The CG received no VR-based interventions. Data were collected using a self-administered questionnaire before and immediately after each intervention. We performed generalized estimating equations to compare the responses. (3) Results: The EG exhibited a more significant improvement in oral care-related knowledge, attitude, self-efficacy, and intention at the 6-week follow-up than the CG. The students' intention to assist the elderly in using interdental brushes (ß = 0.91), with soft tissue cleaning (ß = 0.53), and with oral desensitization (ß = 0.53), and to have regular dental visits (ß = 0.61) improved significantly at the 6-week follow-up. (4) Conclusions: VR training positively affected students' knowledge, attitude, self-efficacy, and intentions on providing oral healthcare to disabled elderly persons.

6.
ACR Open Rheumatol ; 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1712012

ABSTRACT

OBJECTIVE: Patients with anti-melanoma-differentiation-associated 5 (anti-MDA5)-positive dermatomyositis (DM) share several striking similarities to patients with SARS-CoV-2. Our objective was to assess the prevalence of anti-angiotensin converting enzyme-2 (ACE2) immunoglobulin M (IgM) antibodies, found in patients with severe SARS-CoV-2, in two independent anti-MDA5-positive DM cohorts. METHODS: Anti-ACE2 IgM antibodies were assayed by enzyme-linked immunosorbent assay (ELISA) in two anti-MDA5-positive DM cohorts: a predominantly outpatient North American cohort (n = 52) and a Japanese cohort enriched for new-onset disease (n = 32). Additionally, 118 patients with SARS-CoV-2 with a spectrum of clinical severity were tested for anti-MDA5 antibodies by ELISA. RESULTS: Five of fifty-two (9.6%) North American patients and five of thirty-two (15%) Japanese patients were positive for anti-ACE2 IgM. In the North American cohort, all five patients with anti-ACE2 IgM antibodies had proximal muscle weakness, had interstitial lung disease, were significantly more likely to receive pulse dose methylprednisolone (80% vs 30%, P = 0.043), and had worse forced vital capacity (median 59% predicted vs 78%, P = 0.056) compared with the anti-ACE2-IgM-negative group. In the Japanese cohort, all five anti-ACE2-IgM-positive patients also required pulse dose methylprednisolone, and three of five (60%) patients died. Japanese patients with anti-ACE2 IgM had significantly worse oxygenation, as defined by a lower partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (233 vs 390, P = 0.021), and a higher alveolar-arterial oxygenation gradient (91 vs 23 mm Hg, P = 0.024) than the IgM-negative group. CONCLUSION: We describe anti-ACE2 IgM autoantibodies in two independent cohorts with anti-MDA5-positive DM. These autoantibodies may be biomarkers for severe disease and provide insight into disease pathogenesis.

7.
Eur Radiol ; 2022 Feb 19.
Article in English | MEDLINE | ID: covidwho-1707890

ABSTRACT

OBJECTIVES: We aimed to develop deep learning models using longitudinal chest X-rays (CXRs) and clinical data to predict in-hospital mortality of COVID-19 patients in the intensive care unit (ICU). METHODS: Six hundred fifty-four patients (212 deceased, 442 alive, 5645 total CXRs) were identified across two institutions. Imaging and clinical data from one institution were used to train five longitudinal transformer-based networks applying five-fold cross-validation. The models were tested on data from the other institution, and pairwise comparisons were used to determine the best-performing models. RESULTS: A higher proportion of deceased patients had elevated white blood cell count, decreased absolute lymphocyte count, elevated creatine concentration, and incidence of cardiovascular and chronic kidney disease. A model based on pre-ICU CXRs achieved an AUC of 0.632 and an accuracy of 0.593, and a model based on ICU CXRs achieved an AUC of 0.697 and an accuracy of 0.657. A model based on all longitudinal CXRs (both pre-ICU and ICU) achieved an AUC of 0.702 and an accuracy of 0.694. A model based on clinical data alone achieved an AUC of 0.653 and an accuracy of 0.657. The addition of longitudinal imaging to clinical data in a combined model significantly improved performance, reaching an AUC of 0.727 (p = 0.039) and an accuracy of 0.732. CONCLUSIONS: The addition of longitudinal CXRs to clinical data significantly improves mortality prediction with deep learning for COVID-19 patients in the ICU. KEY POINTS: • Deep learning was used to predict mortality in COVID-19 ICU patients. • Serial radiographs and clinical data were used. • The models could inform clinical decision-making and resource allocation.

8.
PLoS One ; 16(10): e0259153, 2021.
Article in English | MEDLINE | ID: covidwho-1699423

ABSTRACT

PURPOSE: To determine the effects of statins and steroids on the risk of coronary artery disease (CAD) and stroke in patients with interstitial lung disease and pulmonary fibrosis (ILD-PF). METHODS: We retrospectively enrolled patients with ILD-PF who were using statins (statin cohort, N = 11,567) and not using statins (nonstatin cohort, N = 26,159). Cox proportional regression was performed to analyze the cumulative incidence of CAD and stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of CAD and stroke were determined after sex, age, and comorbidities, as well as the use of inhaler corticosteroids (ICSs), oral steroids (OSs), and statins, were controlled for. RESULTS: Compared with those of patients without statin use, the aHRs (95% CIs) of patients with statin use for CAD and ischemic stroke were 0.72 (0.65-0.79) and 0.52 (0.38-0.72), respectively. For patients taking single-use statins but not ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.72 (0.65-0.79)/0.69 (0.61-0.79) and 0.54 (0.39-0.74)/0.50 (0.32-0.79), respectively. For patients using ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.71 (0.42-1.18)/0.74 (0.64-0.85) and 0.23 (0.03-1.59)/0.54 (0.35-0.85), respectively. CONCLUSIONS: The findings demonstrate that statin use, either alone or in combination with OS use, plays an auxiliary role in the management of CAD and ischemic stroke in patients with ILD-PF.


Subject(s)
Coronary Artery Disease/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lung Diseases, Interstitial/complications , Pulmonary Fibrosis/complications , Steroids/therapeutic use , Stroke/epidemiology , Coronary Artery Disease/complications , Coronary Artery Disease/prevention & control , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Incidence , Male , Middle Aged , Steroids/administration & dosage , Stroke/complications , Stroke/prevention & control
9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309023

ABSTRACT

Background: The COVID-19 pandemic is a major health crisis has led to adverse mental health consequences in the general public, medical staff, and individual in self isolation. In order to stop transmission of the virus and save lives, Fangcang shelter hospitals were developed and used for the first time in China. However, there is no research on mental health problems in Fangcang shelter hospitals patients during the COVID-19 outbreak. The aim of this study was to survey the prevalence and major influencing factors of anxiety, depression among the hospitalized Coronavirus Disease 2019 (COVID-19) cases in Fangcang shelter hospital. Methods From February 23rd, 2020, to February 26th, 2020, we obtained the information of demographic data, clinical symptoms, and assessed the mental health status, sleep quality by using an online questionnaire including self-rating anxiety scale (SAS), self-rating depressive scale (SDS) and pittsburgh sleep quality index (PSQI) at Jianghan Fangcang shelter hospital. We assessed the prevalence of anxiety, depression symptoms and poor sleep quality via the scores of SAS, SDS and PSQI. We explored the influencing factors of anxiety and depression in COVID-19 patients using multivariable logistic regression models. Results We collected data from 307 COVID-19 patients in Jianghan Fangcang shelter hospital. The prevalence of anxiety, depression symptoms were 18.6% and 13.4%, respectively. Poor Sleep quality, number of current physical symptoms ≥ 2 were independent risk factors for anxiety symptoms ( P  < 0.05);female, family member confirmed COVID-19, number of current physical symptoms ≥ 2 were independent risk factors for depression symptoms ( P  < 0.05). PSQI scores were significant positively associate with SAS scores and SDS scores ( P ༜ 0.05). Conclusions Anxiety and depression are common among the COVID-19 patients in Fangcang shelter hospital. Those with more current physical symptoms, poor sleep quality are more likely to have anxiety. Females, those with their family members diagnosed with COVID-19, more current physical symptoms are more vulnerable to depression symptom. Our findings can be used to formulate targeted psychological interventions to reduce adverse psychological impacts in Fangcang shelter hospital during the outbreak of epidemic disease in the future.

10.
J Biol Chem ; 298(3): 101658, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1654686

ABSTRACT

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely affected human lives around the world as well as the global economy. Therefore, effective treatments against COVID-19 are urgently needed. Here, we screened a library containing Food and Drug Administration (FDA)-approved compounds to identify drugs that could target the SARS-CoV-2 main protease (Mpro), which is indispensable for viral protein maturation and regard as an important therapeutic target. We identified antimalarial drug tafenoquine (TFQ), which is approved for radical cure of Plasmodium vivax and malaria prophylaxis, as a top candidate to inhibit Mpro protease activity. The crystal structure of SARS-CoV-2 Mpro in complex with TFQ revealed that TFQ noncovalently bound to and reshaped the substrate-binding pocket of Mpro by altering the loop region (residues 139-144) near the catalytic Cys145, which could block the catalysis of its peptide substrates. We also found that TFQ inhibited human transmembrane protease serine 2 (TMPRSS2). Furthermore, one TFQ derivative, compound 7, showed a better therapeutic index than TFQ on TMPRSS2 and may therefore inhibit the infectibility of SARS-CoV-2, including that of several mutant variants. These results suggest new potential strategies to block infection of SARS-CoV-2 and rising variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Aminoquinolines , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Molecular Docking Simulation , Pandemics , Protease Inhibitors/pharmacology , Virus Internalization
11.
J Virol ; 96(1): e0125321, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1639525

ABSTRACT

Over the past 20 years, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2 emerged, causing severe human respiratory diseases throughout the globe. Developing broad-spectrum drugs would be invaluable in responding to new, emerging coronaviruses and to address unmet urgent clinical needs. Main protease (Mpro; also known as 3CLpro) has a major role in the coronavirus life cycle and is one of the most important targets for anti-coronavirus agents. We show that a natural product, noncovalent inhibitor, shikonin, is a pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus (HCoV)-HKU1, HCoV-NL63, and HCoV-229E with micromolar half maximal inhibitory concentration (IC50) values. Structures of the main protease of different coronavirus genus, SARS-CoV from the betacoronavirus genus and HCoV-NL63 from the alphacoronavirus genus, were determined by X-ray crystallography and revealed that the inhibitor interacts with key active site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses as well as emerging coronaviruses of the future. Given the importance of the main protease for coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents. IMPORTANCE The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anti-coronavirus agents. We solved the crystal structures of the main protease of SARS-CoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/chemistry , Catalytic Domain , Coronavirus/classification , Coronavirus/enzymology , Coronavirus 3C Proteases/chemistry , Crystallography, X-Ray , Molecular Docking Simulation , Naphthoquinones/chemistry , Protein Binding
12.
Preprint in English | bioRxiv | ID: ppbiorxiv-476892

ABSTRACT

Omicron, a newly emerging SARS-CoV-2 variant, carried a large number of mutations in the spike protein leading to an unprecedented evasion from many neutralizing antibodies (nAbs). Here, we performed a head-to-head comparison of Omicron with other existing highly evasive variants in terms of their reduced sensitivities to antibodies, and found that Omicron variant is significantly more evasive than Beta and Mu variants. Of note, some key mutations occur in the conserved epitopes identified previously, especially in the binding sites of Class 4 nAbs, contributing to the increased Ab evasion. We also reported a broadly nAb (bnAb), VacW-209, which effectively neutralized all tested SARS-CoV-2 variants and even SARS-CoV. Finally, we determined six cryo-electron microscopy structures of VacW-209 complexed with the spike ectodomains of wild-type, Delta, Mu, C.1.2, Omicron, and SARS-CoV, and revealed the molecular basis of the broadly neutralizing activities of VacW-209 against SARS-CoV-2 variants. Overall, Omicron has once again raised the alarm over virus variation with significantly compromised neutralization. BnAbs targeting more conserved epitopes among variants will continue to play a key role in pandemic control and prevention. One sentence summaryStructural and functional analyses reveal that a human antibody named VacW-209 confers broad neutralization against SARS-CoV-2 variants including Omicron by recognizing a highly conserved epitope.

13.
Acad Radiol ; 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1620430

ABSTRACT

RATIONALE AND OBJECTIVES: The coronavirus pandemic upended in-person radiology education and led to a transition to virtual platforms. We needed a new method to monitor lecture attendance, previously relying on a physical badge system. Our goal was to develop and implement a virtual conference attendance system that is user-friendly, automated, useable in any virtual conference environment, and accurate. MATERIALS AND METHODS: We developed a web-based platform to serve as a virtual conference attendance tracking and evaluation platform. Daily, the application synchronizes with our lecture calendar to identify scheduled conferences and generates a unique attendance link for each event. The link is automatically posted in the conference chat and attendees must be logged in by the time it is posted to click the link, prompting single sign-on authentication. We integrated the system with resident schedules to excuse residents when appropriate. Real-time attendance reports are accessible in a user-friendly dashboard with a 5-star lecture review and comment system. We surveyed residents on satisfaction with the application after 1-year of use. RESULTS: Over the 2020-2021 academic year, we registered 376 conferences with 5,040 virtual swipes from 65 users. Once set up, virtual swipes take seconds to perform with minimal disruption to the conference. Average satisfaction for the platform was rated as 4.69 on a scale of 1 to 5. All respondents agreed or strongly agreed that use of the platform should be continued for future years, with 85% strongly agreeing. CONCLUSION: We developed an online platform for radiology conference attendance logging and evaluation, designed for virtual conferences.

14.
Infect Chemother ; 53(4): 730-740, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1595379

ABSTRACT

INTRODUCTION: Zika virus (ZIKV), a mosquito-borne flavivirus, causes the outbreaks of Latin America in 2015 - 2016, with the incidence of neurological complications. Sunitinib malate, an orally bioavailable malate salt of the tyrosine kinase inhibitor, is suggested as a broad-spectrum antiviral agent against emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. MATERIALS AND METHODS: This study investigated the antiviral efficacy and antiviral mechanisms of sunitinib malate against ZIKV infection using cytopathic effect reduction, virus yield, and time-of-addition assays. RESULTS: Sunitinib malate concentration-dependently reduced ZIKV-induced cytopathic effect, the expression of viral proteins, and ZIKV yield in supernatant with 50% inhibitory concentration (IC50) value of 0.015 µM, and the selectivity index of greater than 100 against ZIKV infection, respectively. Sunitinib malate had multiple antiviral actions during entry and post-entry stages of ZIKV replication. Sunitinib malate treatment at entry stage significantly reduced the levels of ZIKV RNA replication with the reduction of (+) RNA to (-) RNA ratio and the production of new intracellular infectious particles in infected cells. The treatment at post-entry stage caused a concentration-dependent increase in the levels of ZIKV (+) RNA and (-) RNA in infected cells, along with enlarging the ratio of (+) RNA to (-) RNA, but caused a pointed increase in the titer of intracellular infectious particles by 0.01 and 0.1 µM, and a substantial decrease in the titer of intracellular infectious particles by 1 µM. CONCLUSION: The study discovered the antiviral actions of sunitinib malate against ZIKV infection, demonstrating a repurposed, host-targeted approach to identify potential antiviral drugs for treating emerging and global viral diseases.

15.
Vaccines (Basel) ; 9(12)2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1580390

ABSTRACT

Large clinical trials have proven the efficacy of the COVID-19 vaccine, and the number of studies about the effectiveness rapidly grew in the first half of the year after mass vaccination was administrated globally. This rapid review aims to provide evidence syntheses as a means to complement the current evidence on the vaccine effectiveness (VE) against various outcomes in real-world settings. Databases (PubMed, EMBASE, and MedRxiv) were searched up to 30 June 2021, (PROSPERO ID: 266866). A total of 39 studies were included, covering over 15 million participants from 11 nations. Among the general population being fully vaccinated, the VE against symptomatic SARS-CoV-2 infection was estimated at 89-97%, 92% (95% CI, 78-97%), and 94% (95% CI, 86-97%) for BNT162b2, ChAdOx1, and mRNA-1273, respectively. As for the protective effects against B.1.617.2-related symptomatic infection, the VE was 88% (95% CI, 85.3-90.1%) by BNT162b2 and 67.0% (95% CI, 61.3-71.8%) by ChAdOx1 after full vaccination. This review revealed a consistently high effectiveness of certain vaccines among the general population in real-world settings. However, scarce data on the major variants of SARS-CoV-2 and the shortness of the study time may limit the conclusions to the mRNA vaccines and ChAdOx1.

16.
Mathematical Problems in Engineering ; 2021, 2021.
Article in English | ProQuest Central | ID: covidwho-1546590

ABSTRACT

In the wave of Industry 4.0, GPS sports watches are redeveloping towards digitization and intelligence. Whether the information is correct and real-time, operation interfaces easy to use and the displayed information easy to understand have become issues that consumers and manufacturers emphasize. Thus, this study investigated the effects of output quality and result demonstrability on the perceived usefulness of GPS sports watches with participants of the 2020 Taiwan International Triathlons as the research subjects. In total, 280 respondents, who participated in the 2020 Taiwan International Triathlon, were selected by purposive sampling for a questionnaire survey. The statistical software SPSS was employed to file the data, and the statistical software of AMOS was adopted to analyze the correlation among variables. According to the results, (1) output quality has significantly positive effects on perceived usefulness;(2) result demonstrability has significantly positive effects on perceived usefulness;(3) perceived ease of use has significantly positive effects on perceived usefulness;(4) perceived ease of use has significantly positive effects on behavioral intention to use;and (5) perceived usefulness has significantly positive effects on behavioral intention to use.

17.
Infect Genet Evol ; 97: 105164, 2022 01.
Article in English | MEDLINE | ID: covidwho-1536954

ABSTRACT

The widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuously impacts our economic and public health. The potential of emerging variants to increase transmissibility and evade vaccine-induced immunity lets us put more effort to research on viral mutations and explore the pathogenic haplotypes. In this study, we characterized the haplotype and sub-haplotype diversity of SARS-CoV-2 global variants in January-March and the areas with low and high COVID19 vaccination rates in May 2021 by analyzing viral proteome of complete genome sequences published. Phylogenetic tree analysis of the proteomes of SARS-CoV-2 variants with Neighbor-Joining and Maximum Parsimony methods indicated that haplotype 2 variant with nsp12 P323L and Spike D614G was dominant (98.81%), including new sub-haplotypes 2A_1 to 2A_3, 2B_1 to 2B_3, and 2C_1 to 2C_2 emerged post-one-year COVID-19 outbreak. In addition, the profiling of sub-haplotypes indicated that sub-haplotype 2A_1 with the mutations at N501Y, A570D, D614G, P681H, T716I, S982A, and D118H in Spike was over 58% in May 2021 in the high partly vaccinated rate group (US, Canada, and Germany). Meanwhile, the new haplotype 2C_3 bearing the mutations at EFR156-158del, T19R, A222V, L452R, T478K, and D614G in Spike occupied over 54.8% in May 2021 in the low partly vaccinated rate group (India, Malaysia, Taiwan, and Vietnam). Sub-haplotypes 2A_1 and 2C_3 had a meaningful alternation of ACE2-specific recognition site, neutralization epitopes, and furin cleavage site in SARS-CoV-2 Spike protein. The results discovered the haplotype diversity and new sub-haplotypes of SARS-CoV-2 variants post one-year pandemic in January-March 2021, showing the profiles of sub-haplotypes in the groups with low and high partly vaccinated rates in May 2021. The study reports the emergence of new SARS-CoV-2 sub-haplotypes during ongoing pandemic and vaccination in early 2021, which might help inform the response to vaccination strategies.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/epidemiology , COVID-19/prevention & control , Mutation , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Americas/epidemiology , Amino Acid Substitution , Asia/epidemiology , COVID-19/immunology , COVID-19/transmission , Epidemiological Monitoring , Europe/epidemiology , Gene Expression , Genome, Viral , Haplotypes , Humans , Immune Evasion , Models, Molecular , Phylogeny , Protein Interaction Domains and Motifs , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vaccination Coverage/statistics & numerical data
18.
Crit Care Med ; 49(12): 2058-2069, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1528201

ABSTRACT

OBJECTIVES: To provide updated information on the burdens of sepsis during acute inpatient admissions for Medicare beneficiaries. DESIGN: Analysis of paid Medicare claims via the Centers for Medicare and Medicaid Services DataLink Project. SETTING: All U.S. acute-care hospitals, excluding federally operated hospitals (Veterans Administration and Defense Health Agency). PATIENTS: All Medicare beneficiaries, January 2012-February 2020, with an explicit sepsis diagnostic code assigned during an inpatient admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The count of Medicare Part A/B (fee-for-service) plus Medicare Advantage inpatient sepsis admissions rose from 981,027 (CY2012) to 1,700,433 (CY 2019). The proportion of total admissions with sepsis in the Medicare Advantage population rose from 21.43% to 35.39%, reflecting the increasing beneficiary proportion enrolled in Medicare Advantage. In CY2019, 6-month mortality rates in Medicare fee-for-service beneficiaries for sepsis continued to decline, but remained high: 59.9% for septic shock, 35.5% for severe sepsis, 30.8% for sepsis attributed to a specific organism, and 26.5% for unspecified sepsis. Total fee-for-service-only inpatient hospital costs rose from $17.79B (CY2012) to $22.98B (CY2019). We estimated that the aggregate cost of sepsis hospital care for the entire U.S. population was at least $57.47B in 2019. Inclusion of 14 months' (January 2019-February 2020) newer data exposed new trends: the cost per patient, number of admissions, and fraction of patients with sepsis labeled as present on admission inflected around November 2015, coincident with the change to International Classification of Diseases, 10th Edition, and introduction of the Severe Sepsis and Septic Shock Management Bundle (SEP-1) metric. CONCLUSIONS: Sepsis among Medicare beneficiaries precoronavirus disease 2019 imposed immense burdens upon patients, their families, and the taxpayers.


Subject(s)
Medicare/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Sepsis/diagnosis , Fee-for-Service Plans/economics , Hospitalization/statistics & numerical data , Humans , Sepsis/economics , Sepsis/epidemiology , United States/epidemiology
19.
J Food Saf ; : e12932, 2021 Oct 03.
Article in English | MEDLINE | ID: covidwho-1450564

ABSTRACT

COVID-19 has brought speculations on potential transmission routes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the pandemic. It is reported that the main route of virus transmission to be person-to-person by respiratory droplets; however, people have raised concerns on the possible transmission of SARS-CoV-2 to humans via food and packaging and its potential effects on food safety. This review discusses food safety issues in the COVID-19 pandemic and reveals its possible transmission in cold-chain food. The first outbreak of COVID-19 in late 2019 was associated with a seafood market in Wuhan, China, while the second outbreak of COVID-19 in June 2020 was also related to a seafood market in Beijing, China. As of 2020, several frozen seafood products linked with SARS-CoV-2 have been reported in China. According to the current survey and scientific studies, the risk of infection by SARS-CoV-2 from cold-chain food, food products, and food packaging is thought to be very low. However, studies on food cold chain contamination have shown that SARS-CoV-2 remained highly stable under refrigerated (4°C) and even in freezing conditions (-10 to -80°C). Since one mode of SARS-CoV-2 transmission appears to be touching contaminated surfaces, it is important to clean and sanitize food contact surfaces properly. Understanding food safety hazard risks is essential to avoid potential negative health effects and SARS-CoV-2 transmission in the food supply chain during the COVID-19 pandemic.

20.
Acta Crystallogr F Struct Biol Commun ; 77(Pt 10): 348-355, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1450488

ABSTRACT

Human coronavirus NL63 (HCoV-NL63), which belongs to the genus Alphacoronavirus, mainly infects children and the immunocompromized and is responsible for a series of clinical manifestations, including cough, fever, rhinorrhoea, bronchiolitis and croup. HCoV-NL63, which was first isolated from a seven-month-old child in 2004, has led to infections worldwide and accounts for 10% of all respiratory illnesses caused by etiological agents. However, effective antivirals against HCoV-NL63 infection are currently unavailable. The HCoV-NL63 main protease (Mpro), also called 3C-like protease (3CLpro), plays a vital role in mediating viral replication and transcription by catalyzing the cleavage of replicase polyproteins (pp1a and pp1ab) into functional subunits. Moreover, Mpro is highly conserved among all coronaviruses, thus making it a prominent drug target for antiviral therapy. Here, four crystal structures of HCoV-NL63 Mpro in the apo form at different pH values are reported at resolutions of up to 1.78 Å. Comparison with Mpro from other human betacoronaviruses such as SARS-CoV-2 and SARS-CoV reveals common and distinct structural features in different genera and extends knowledge of the diversity, function and evolution of coronaviruses.


Subject(s)
Coronavirus NL63, Human/chemistry , Crystallization/methods , Crystallography, X-Ray/methods , Humans , Hydrogen-Ion Concentration , Protein Conformation
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