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1.
researchsquare; 2023.
Preprint en Inglés | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2635774.v1

RESUMEN

Background: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity.  We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. Methods: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. Discussion: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 hours and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific, prevalent pathogens as a cause of acute illness. Study Registration: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.


Asunto(s)
Enfermedad Aguda , Convalecencia
2.
Journal of Marine Science and Engineering ; 10(7):991, 2022.
Artículo en Inglés | MDPI | ID: covidwho-1938872

RESUMEN

Due to COVID-19 barriers, the needs of international container ports have become more important than in the past. Therefore, it is very critical and essential for the scientific developments of port-logistics. To gain the scientific developments of port logistics, effective and efficient evaluation methods for decision-making are indispensable, especially for assessing service performance of international container ports based on dependent evaluation criteria (DEC). Among numerous decision-making methods, technique for order preference by similarity to ideal solution (TOPSIS) was often expanded under fuzzy environments into fuzzy multi-criteria decision-making (FMCDM) to preserve imprecise messages. The FMCDM was able to be associated with quality function deployment (QFD) into a hybrid method to solve problems with DEC. To gain more messages, QFD and TOPSIS are combined and then expanded under interval-valued fuzzy environment (IVFE) to solve a FMCDM problem with DEC. Practically, evaluating service performance of international container ports in Taiwan and the surrounding sea areas is considered a problem with DEC because the related evaluation criteria are partially connected. By the hybrid method of combining QFD with TOPSIS under IVFE, international container ports with DEC are effectively and efficiently evaluated for service performance, and more insights are gained than the past for establishing essential fundamentals in recent scientific developments of port logistics on account of breaking down COVID-19 barriers.

3.
researchsquare; 2022.
Preprint en Inglés | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1892293.v1

RESUMEN

Background:It is well recognized that the Beijing 2022 Olympics will be the second Games held amid the COVID-19 pandemic, a condition that has impacted millions of lives from every nation, moreover, to a certain extent, it has altered the way sporting activities operate.And there is a lack of knowledge on injury risk and illness occurrence in elite winter sport athletes amid the COVID-19 pandemic.Objective:To describe the incidence of injuries and illnesses sustained during the XXIV Olympic Winter Games, in Beijing held from February 4 to 20, 2022.Methods:We recorded the daily number of injuries and illnesses among athletes reported by Beijing 2022 medical staff in the polyclinic, medical venues, and ambulance.Results:In total, 2897 athletes from 91 nations experienced injury or illness. Beijing 2022 medical staff reported 326 injuries and 80 illnesses, equaling 11.3 injuries and 2.8 illnesses per 100 athletes over the 17-day period. Altogether, 11% of the athletes incurred at least one injury and nearly 3% at least one illness. The number of injured athletes was highest in the skating sports (n=104), followed by alpine skiing (n=53), ice track (n=37), freestyle skiing (n=36), and ice hockey (n=35) and was lowest in the Nordic skiing disciplines (n=20). Of the 326 injuries, 14 (4.3%) led to an estimated absence from training or competition of more than 1 week. A total of 52 injured athletes were transferred to hospitals for further care. The number of athletes with illness (n=80) was highest for skating (n=33) and Nordic skiing (n=22). A total of 50 illnesses (62.5%) were attributed to the department of dentistry/ophthalmology/otolaryngology, and the most common cause of illness was other causes, including preexisting illness and drugs (n=52, 65%).Conclusions: Overall, 11% of athletes incurred at least one injury during the Games, which is similar to the figures during the Olympic Winter Games in 2014 and 2018. Regarding illness, 2% of athletes were affected, which is approximately three-fold lower than the Olympic Winter Games in 2018. 


Asunto(s)
COVID-19
4.
Front Public Health ; 10: 892773, 2022.
Artículo en Inglés | MEDLINE | ID: covidwho-1879482

RESUMEN

Objective: To explore the impact of the COVID-19 pandemic on hospital business and the contribution of Internet healthcare to hospital operations during the epidemic by analyzing the degree of impact on major business indicators. Methods: The three-year period from 2019 to 2021 was compared and analyzed, and the main medical business indicators such as outpatient and emergency visits, inpatients, operations, patient improvement rate, cure rate and fatality rate in tertiary hospitals were compared and analyzed, and the impact of the epidemic on medical services and hospital operation was analyzed. degree and the impact of Internet medical development on medical service capacity. Results: During the outbreak of COVID-19, the number of hospital outpatient and emergency visits, inpatients, and operations decreased significantly; after the normalization of the epidemic, the main medical business indicators such as outpatient and emergency visits, inpatients, and operations gradually returned to pre-epidemic levels; patient improvement rate, the cure rate and mortality rate and other indicators did not change significantly. During the epidemic period, the number of visits to the Internet outpatient clinic has increased significantly, which has significantly improved the hospital's medical service capacity. Conclusion: With the normalization of epidemic prevention and control, the main business indicators of Tianjin tertiary hospitals have gradually recovered. The operation of Internet medical care during the epidemic has changed the management and operation mode of the hospital to a certain extent, improved the main business indicators of the hospital, and eased the pressure on the hospital's economic operation.


Asunto(s)
COVID-19 , Telemedicina , COVID-19/epidemiología , Humanos , Internet , Pandemias , SARS-CoV-2 , Centros de Atención Terciaria
5.
IEEE Transactions on Automation Science & Engineering ; 19(2):620-631, 2022.
Artículo en Inglés | Academic Search Complete | ID: covidwho-1788782

RESUMEN

In the coronavirus epidemic, many Chinese hospitals have established buffer zones to prevent the spread and transmission of the virus. The buffer zone is a monitored and separate area where the patients who need hospitalizations after the quick treatments in the emergency department can temporarily wait for the Covid-19 test and receive some healthcare services to stabilize their conditions. Because the beds in the buffer zones are limited, the managers face the patient admission control problem for the buffer zone. This management and control problem is challenging since the patient arrivals are uncertain, and the patients’ conditions are different. In this paper, we build the infinite- and finite-horizon Markov decision process (MDP) models for this problem. We use the uniformization method to discretize the patient flow. We propose various iteration algorithms to solve the MDP models and obtain the optimal and threshold policies. Numerical experiments validate the advantages of the policies obtained by the algorithms in this paper over the current policies of hospitals. Note to Practitioners—The ongoing COVID-19 pandemic has been causing enormous damage to people’s health, jobs, and well-being. COVID-19 has affected almost all countries globally and has changed the operation mode of the healthcare system, especially the hospitals. The hospitals are the frontlines of healthcare service and the battle with the COVID-19 pandemic. This article is motivated by our collaborations with hospitals in Shanghai, China. In China, many hospitals establish buffer zones: a monitored area where the patients who need hospitalizations after the quick treatments in the emergency department can temporarily wait for the Covid-19 test and receive some healthcare services to stabilize their conditions. Because the zone’s capacity is limited, the managers must make dynamic patient admission control decisions according to multiple factors, such as patients’ health conditions and the usage of beds in the zone. We propose two MDP models to solve this complex problem. Several iteration algorithms are designed to solve the MDP models and obtain the optimal and threshold policies. Based on hospitals’ real-life data, we show the methods presented in this paper can help hospital managers make more reasonable decisions. Although we focus on the hospital’s buffer zone in China, the methodology and approach for this problem can be extended to other practical hospital management scenarios in the coronavirus pandemic. For example, For example, some hospitals have admission control problems for coronavirus patients due to hospital capacity limitations. The hospital has to decide if a patient is accepted as an inpatient or suggested to home quarantine. In such a case, the admission control problem can also be solved by the methodologies in the paper. [ FROM AUTHOR] Copyright of IEEE Transactions on Automation Science & Engineering is the property of IEEE and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

6.
Pharmacological Research - Modern Chinese Medicine ; : 100085, 2022.
Artículo en Inglés | ScienceDirect | ID: covidwho-1763936

RESUMEN

The vascular niche is a microenvironment located around capillaries and is mainly composed of endothelial cells, pericytes, macrophages, lymphocytes, mesenchymal stem cells, and hematopoietic stem cells. Studies have found that the vascular niche not only functions to regulate cell growth and differentiation in normal tissues, but also has an important role in regulating fibrosis in various organs and tissues in disease states. Coronavirus disease 2019 (COVID-19) is a systemic disease that broke out in 2019, caused by SARS-CoV-2 infection, which results in pulmonary inflammation, systemic multi-organ damage, and an inflammatory cytokine storm. Recently, the vascular niche has been found to play a role in COVID-19-related multi-organ damage. In this review, we introduce the important role of the vascular niche in organ fibrosis and COVID-19-related organ damage, summarize some of the cellular signaling pathways in the vascular niche that promote fibrosis, and discuss the treatment of organ fibrosis in Traditional Chinese medicine and Western medicine.

7.
Frontiers in psychology ; 13, 2022.
Artículo en Inglés | EuropePMC | ID: covidwho-1733447

RESUMEN

Background In the early days of COVID-19 outbreak, the normally orderly health system was severely challenged by large numbers of feverish patients and shortage of healthcare workers. The outbreak played a harmful role in the mental health of these healthcare workers. Objective We aim to assess the prevalence of moderate or severe anxiety and depression symptoms (ADSs) of healthcare workers in different regions during COVID-19 disaster and identify the potential risk factors. Methods We did a cross-sectional study on ADS of healthcare workers in epicenter-Hubei province and regions in lower epidemic-other provinces by questionnaire online. The data of ADS, the demographic characteristics, occupational exposure, physical condition, family situation, and coping styles were collected and analyzed. Results A total of 24.68% of the respondents had experienced moderate or severe ADS. Moderate or severe ADSs were in a higher prevalence in Hubei (32.39%) than other provinces (18.22%). Suspicious symptoms on their own and in family members were independent risk factors of moderate or severe ADS of all health workers. Working on the frontline was the independent risk factor for participants in Hubei province, whereas quarantine was the independent risk factor for those in other provinces. Moreover, among all participants, those with negative coping style were more than four times more likely to have moderate or severe ADS than those with positive coping style. Conclusion Moderate or severe ADSs were in a higher prevalence in healthcare workers of Hubei province during COVID-19 outbreak. The coping style may have major impact on ADS in such situation.

9.
researchsquare; 2022.
Preprint en Inglés | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1413625.v1

RESUMEN

Purpose: Multisystem inflammatory syndrome in children, which has overlapping clinical features with Kawasaki disease (KD), has generated considerable interest in the relationship between KD and infectious diseases during the ongoing global outbreak of coronavirus disease 2019. However, few studies have focused on the relationship between KD and concomitant infection, and reports on the relationship between infections and recovery from coronary artery aneurysms (CAA) are even rarer. Methods: : Patients were classified into case and control groups according to the results of their pathogen examinations, and the baseline characteristics of the two groups were compared. The Kaplan–Meier survival analysis was used to compare the medium-term recovery time of CAA between patients with and without infections, and multivariable analyses were performed to evaluate potential risk factors associated with CAA without recovery between 1 and 2 years of follow-up. Results: : A total of 353 pediatric patients with KD were included, of whom 83 (23.5%) had confirmed co-infection. There were no significant differences in patients’ response to treatment and coronary artery outcome when compared between patients with and without infections. Among the 90 patients diagnosed with CAA, 20 (22.2%) had confirmed co-infection, and no significant differences were observed in coronary artery changes from baseline at 2 weeks, 4 weeks, and 3 months in patients with CAA with and without infections. The estimated median time (6 months, 95%CI:1.920–10.080) was higher in the CAA co-infected group than in the CAA non-infected group (3 months, 95%CI:2.366–3.634), with no significant difference. Multivariate analysis revealed that a high Z-score of the coronary artery internal diameter at 1 month after onset was significantly associated with CAA without recovery. The Z score of the left main coronary artery was ≥3.215 with an 89% sensitivity and 77% specificity in predicting CAA without recovery within 1 year of onset. The Z score of the right coronary artery was ≥3.845 with a 64% sensitivity and 98% specificity in predicting CAA without recovery within 1 year of onset and with an 83% sensitivity and 88% specificity within 2 years of onset. Conclusions: : Concomitant infection with KD diagnosis did not affect the patients’ response to IVIG treatment and coronary artery outcome when compared with patients without infections; however, the time to coronary artery normalization was not notably prolonged in CAA patients with infections, but a larger maximum Z score at 1 month after onset was a risk factor significantly associated with coronary artery dilatation without recovery within 2 years of onset.


Asunto(s)
Síndrome Mucocutáneo Linfonodular , Enfermedades Transmisibles , Aneurisma Coronario , COVID-19
10.
Alexandria Engineering Journal ; 2021.
Artículo en Inglés | ScienceDirect | ID: covidwho-1471860

RESUMEN

Under the dispute between China and the United States, the international field of public opinion is dominated by increasing tensions, and the network rumors triggered by the COVID-19 epidemic are intensifying. In view of the above-mentioned context, this paper focuses on the development and the evolution process of public opinions. Since the evolution of public opinion is often accompanied by the spread and diffusion of information, this paper combines the process of information diffusion with the development process of polarization behavior, and brings in the dynamic network and the timeliness factor of public opinion dissemination, so as to better explore the polarization process of public opinion under the dynamic network. Then, this paper focuses on the analysis of the parameters of the model and through the dynamic adjustment of parameters, finding out the main factors that affect the trend and development of network public opinion. In addition, this paper introduces an actual case, and takes the actual case data as the support to demonstrate the reliability and practical application value of the model. Finally, based on the simulation results and analysis of actual cases, this paper puts forward the corresponding preventive measures to alleviate the polarization behavior of the group.

11.
researchsquare; 2021.
Preprint en Inglés | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-934255.v1

RESUMEN

Background: Although chest computed tomography (CT) is the gold standard for diagnosing the majority of lung conditions, its use in screening patients for coronavirus disease 2019(COVID-19) pneumonia is not recommended. Lung ultrasound (LUS) is an alternative modality. To investigate the characteristics and diagnostic accuracy (DA) of bedside ultrasound for lung lesions in patients with COVID-19 and to determine the factors influencing the DA of lung ultrasound (LUS). Methods: A total of 330 patients with COVID-19 admitted to the hospital between February and March 2020 were retrospectively recruited. The imaging characteristics of LUS and computed tomography (CT) scans were analysed and summarized. DA was calculated using a chest CT scan as the reference standard. Furthermore, a binary logistic regression analysis was conducted to investigate the factors influencing the DA of LUS for interstitial syndrome. Results: The ultrasound findings of COVID-19 patients presented mainly as B lines (195/330, 59.1%), unsmooth or interrupted pleural lines (118/330, 35.8%), consolidation lesions (74/330, 22.4%), and pleural effusion (11/330, 3.33%). Compared with the chest CT scan, the DA of LUS for interstitial syndrome, consolidation, pleural effusion, and pleural thickening were 0.821, 0.927, 0.988, and 0.863, respectively. The diagnostic coincidence rate of LUS and chest CT in the mild, common, severe, and critical groups were 93%, 68.6%, 100%, and 100%, respectively. According to the results of the binary logistic regression, sex, disease duration, experience of the doctor, and involved lobes were independent predictors of the DA for interstitial syndrome. Conclusions: LUS had good diagnostic performance for diagnosing COVID-19 pneumonia, and showed a relatively low DA for interstitial syndrome. Female sex, doctors with less experience, long disease duration, and lesions limited to the upper or lower lobes may decrease the DA.


Asunto(s)
COVID-19 , Infecciones por Coronavirus , Enfermedades Pulmonares , Enfermedades Pulmonares Intersticiales
12.
researchsquare; 2021.
Preprint en Inglés | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-836921.v1

RESUMEN

Aims: : T his study was to evaluate the effects of the home quarantine on pregnancy outcomes of gestational diabetes mellitus (GDM) patients during the COVID-19 outbreak. Methods: : Thecomplete electronic medical records of GDM patients with home quarantine history were collected and classified into the home quarantine group from 24 February 2020 to 24 November 2020. The same period of GDM patients without home quarantine historywas included in the control group from 2018 and 2019. Results: : A total of 1358 GDM patients were included in the analysis, including 484 in 2018, 468 in 2019, and 406 in 2020. GDM patients with home quarantine in 2020 had higher glycemic levels and worse pregnancy outcomes than 2018 and 2019, including higher cesarean section rate,lower Apgar scores, and higher incidence of macrosomia and nuchal cord. More importantly, the second trimester of home quarantine had brought a broader impactto pregnant women and fetuses. Conclusion: Home quarantine has aggravated the condition of GDM pregnant women and brought more adverse pregnancy outcomes during the COVID-19 outbreak. Therefore, we suggested that governments and hospitals should strengthen lifestyle guidance, glucose management, and antenatal care for GDM patients with home quarantine during public health emergencies.


Asunto(s)
COVID-19 , Macrosomía Fetal , Diabetes Gestacional
13.
ssrn; 2021.
Preprint en Inglés | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3905687

RESUMEN

Identifying the host factors influencing the COVID-19 outcome is critical to overcome the global pandemic. The associations between immune phenotypes and the risk of COVID-19 are still poorly understood. We sought to systematically evaluate the causal impact of multiple immune cell traits on COVID-19 susceptibility and its severity using two-sample Mendelian randomization (MR). Genetic variants associated with each immune phenotypes at P < 5×10-8 from genome-wide association studies (GWAS). The GWAS statistics of COVID-19 is from COVID-19 Host Genetics Initiative. Susceptibility and severity were defined as COVID-19 positive and hospitalization versus population controls, respectively. Inverse-variance weighted (IVW) method was used as the main MR analysis, and comprehensive sensitivity analyses were conducted for estimating the robustness. The MR estimates showed that genetically predicted high expression of BAFF-R on B cell was strongly associated with a lower risk of COVID-19 severity. In addition, BAFF-R expression on B cell subsets showed consistent causal relationship with COVID-19 severity, such as its expression on transitional B cell and naïve-mature B cell. Evidence from all sensitivity analyses further supported these associations. In MR analysis for COVID-19 susceptibility, we observed a highly consistent protective role of BAFF-R expression, although the P value was not significant. Moreover, in multivariable MR analyses, adjusting for the effects of other B cell biomarkers displayed similar MR findings. This study provides genetic evidence that the genetically high expression of BAFF-R on B cells decreases the risk of COVID-19 severity.


Asunto(s)
COVID-19
14.
Atmospheric Pollution Research ; : 101111, 2021.
Artículo en Inglés | ScienceDirect | ID: covidwho-1272296

RESUMEN

The contributions of emission reduction and meteorological changes to air quality improvement in Hubei Province (HB) have required assessment in recent years. In this study, the WRF-Chem scenario tests were conducted to evaluate the effect of both the emission and meteorological changes on the winter PM2.5 from 2015 to 2019, especially that of regional transport and local emissions on the PM2.5 variations in HB. The results showed that meteorological changes in January 2019 increased the PM2.5 by 24% relative to January 2015, whereas emissions reduced it by 36%, indicating that emission reduction was vital in improving the air quality in HB. However, the meteorological changes increased the concentration of air pollutants by 10–25% relative to January 2018. This led to a rebound of the observed pollutant concentrations in January 2019, highlighting the importance of meteorological conditions on air pollution. Regional transport of air pollutants contributed to the inter-annual increase of wintertime PM2.5 by 78%, driven purely by meteorology from 2015 to 2019. This indicated that regional PM2.5 transport could aggravate PM2.5 levels in winter over HB with the reduction of air pollutant emissions in China. Additionally, the regional transport of air pollutants contributed to the decrease in PM2.5 in HB by 42%, resulting from the non-local emission reduction during COVID-19 lockdown in winter. This indicates the importance of the regional transport of air pollutants in driving regional changes in the atmospheric environment over China.

15.
researchsquare; 2021.
Preprint en Inglés | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-419305.v1

RESUMEN

The endo-lysosomal pathway plays an important role in pathogen clearance and both bacteria and viruses have evolved complex mechanisms to evade this host system. Here, we describe a novel aspect of coronaviral infection, whereby the master transcriptional regulator of lysosome biogenesis – TFEB – is targeted for proteasomal-mediated degradation upon viral infection. Through mass spectrometry analysis and an unbiased siRNA screen, we identify that TFEB protein stability is coordinately regulated by the E3 ubiquitin ligase subunit DCAF7 and the PAK2 kinase. In particular, viral infection triggers marked PAK2 activation, which in turn, phosphorylates and primes TFEB for ubiquitin-mediated protein degradation. Deletion of either DCAF7 or PAK2 blocks viral-mediated TFEB degradation and protects against viral-induced cytopathic effects. We further derive a series of small molecules that interfere with the DCAF7-TFEB interaction. These agents inhibit viral-triggered TFEB degradation and demonstrate broad anti-viral activities including attenuating in vivo SARS-CoV-2 infection. Together, these results delineate a viral-triggered pathway that disables the endogenous cellular system that maintains lysosomal function and suggest that small molecule inhibitors of the E3 ubiquitin ligase DCAF7 represent a novel class of endo-lysosomal, host-directed, anti-viral therapies.


Asunto(s)
COVID-19
16.
researchsquare; 2021.
Preprint en Inglés | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-358218.v1

RESUMEN

Synthetic biology has been harnessed to create new diagnostic technologies. However, most synthetic biosensors involve error-prone amplification steps and limitations of accuracy in RNA detection. Here, we report a cell-free synthetic biosensing platform, termed as SHARK ( S ynthetic Enzyme S h ift RNA Signal A mplifier R elated Cas13a K nockdown Reaction), to efficiently and accurately amplify RNA signal by leveraging the collateral cleavage of activated Cas13a to regulate cell-free enzyme synthesis. Based on cascade amplification and customized enzyme output, SHARK behaves a broad compatibility in different scenarios. Using a personal glucose meter, we detected 50 copies/μl SARS-CoV-2 on a SHARK-loaded paper. In addition, when combined with machine learning, SHARK can perform bio-computations and thus provide miRNA patterns for cancer diagnosis and staging. SHARK shows characteristics of precise recognition, cascade amplification and customizable signal outputting in one pot comparisons with established assays based on 64 clinical samples, presenting great potential in developing next-generation RNA detection technology.


Asunto(s)
Neoplasias
17.
biorxiv; 2021.
Preprint en Inglés | bioRxiv | ID: ppzbmed-10.1101.2021.03.11.434764

RESUMEN

The global emergence of SARS-CoV-2 has triggered numerous efforts to develop therapeutic options for COVID-19 pandemic. The main protease of SARS-CoV-2 (Mpro), which is a critical enzyme for transcription and replication of SARS-CoV-2, is a key target for therapeutic development against COVID-19. An organoselenium drug called ebselen has recently been demonstrated to have strong inhibition against Mpro and antiviral activity but its molecular mode of action is unknown preventing further development. We have examined the binding modes of ebselen and its derivative in Mpro via high resolution co-crystallography and investigated their chemical reactivity via mass spectrometry. Stronger Mpro inhibition than ebselen and potent ability to rescue infected cells were observed for a number of ebselen derivatives. A free selenium atom bound with cysteine 145 of Mpro catalytic dyad has been revealed by crystallographic studies of Mpro with ebselen and MR6-31-2 suggesting hydrolysis of the enzyme bound organoselenium covalent adduct, formation of a phenolic by-product is confirmed by mass spectrometry. The target engagement of these compounds with an unprecedented mechanism of SARS-CoV-2 Mpro inhibition suggests wider therapeutic applications of organo-selenium compounds in SARS-CoV-2 and other zoonotic beta-corona viruses.


Asunto(s)
COVID-19
18.
Front Psychiatry ; 12: 566241, 2021.
Artículo en Inglés | MEDLINE | ID: covidwho-1116721

RESUMEN

Background: During the coronavirus disease 2019 (COVID-19) pandemic, quarantine as an effective public health measure has been widely used in China and elsewhere to slow down the spread, while high-risk psychological response populations remain under-reported. Objective: The aim of the study is to investigate the depressive and anxiety symptoms among the high-risk individuals quarantined during the COVID-19 pandemic in China. Methods: An online survey was conducted from February 29 to April 10, 2020, among individuals quarantined for at least 2 weeks due to the high-risk exposure. Chinese versions of the nine-item Patient Health Questionnaire (PHQ-9) with a seven-item Generalized Anxiety Disorder (GAD-7) were applied to assess depressive and anxiety symptoms, respectively. Compliance with quarantine and knowledge of COVID-19 was also assessed. An unconditional logistic regression model was performed to identify the correlators. Results: Of the 1,260 participants completing the full survey, 14.0% (95% CI: 12.2-16.1%), 7.1% (95% CI: 5.9-8.7%), and 6.3% (95% CI: 5.1-7.8%) had at least moderate symptoms of depression, anxiety, and a combination of depression and anxiety (CDA), respectively; 14.8% (95% CI: 13.0-16.9%) had at least one condition. Multivariate analysis showed that participants with an undergraduate or above degree were more likely to report depressive (OR = 2.98, 95% CI: 1.56-5.72) and anxiety symptoms (OR = 2.95, 95% CI: 1.14-7.63) than those with middle school education. Those who were unemployed (OR = 0.37, 95% CI: 0.21-0.65 for depression; OR = 0.31, 95% CI: 0.14-0.73 for anxiety), students (OR = 0.14, 95% CI: 0.04-0.48 for depression; OR = 0.11, 95% CI: 0.01-0.85 for anxiety), and more knowledgeable of COVID-19 (OR = 0.84, 95% CI: 0.73-0.96 for depression, OR = 0.82, 95% CI: 0.68-0.98 for anxiety) were less likely to report depressive and anxiety symptoms. Higher quarantine compliance correlated with lower risks of depressive (OR = 0.94, 95% CI: 0.91-0.96) and anxiety symptoms (OR = 0.95, 95% CI: 0.91-0.98). Conclusion: Individuals under quarantine during the COVID-19 pandemic suffered prevalent depressive and anxiety symptoms. Consequently, comprehensive interventional measures, including knowledge dissemination, timely virus tests, and strengthened communication, may minimize quarantine's adverse effects.

19.
medrxiv; 2020.
Preprint en Inglés | medRxiv | ID: ppzbmed-10.1101.2020.12.18.20248447

RESUMEN

Summary Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial. We enrolled 193 subjects infected with SARS-CoV-2 in Ningbo and Zhoushan, Zhejiang, China from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of immunoglobulin M (IgM) and IgG against SARS-CoV-2. Of those, 31 were asymptomatic carriers, 149 were symptomatic patients, and 14 were presymptomatic patients. Compared to symptomatic patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower levels of C-reactive protein and viral load, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients ( P =0.030). The proportion of those persistently seropositive for IgG was higher in COVID-19 patients than in asymptomatic carriers ( P =0.037). Viral load was higher in symptomatic than presymptomatic patients. Viral shedding was longer in presymptomatic patients than in asymptomatic carriers. Conclusively, asymptomatic carriers have a higher antiviral immunity to clear SARS-CoV-2 than do symptomatic patients and this antiviral immunity is not contributable to humoral immunity.


Asunto(s)
COVID-19 , Infecciones por Coronavirus
20.
Chinese Journal of Nosocomiology ; 30(19):2900-2903, 2020.
Artículo en Chino | GIM | ID: covidwho-934882

RESUMEN

OBJECTIVE: To explore the establishment and application of novel coronavirus (COVID-19) pneumonia prevention and control system in general hospitals, to formulate effective prevention and control strategies, so as to provide experience for general hospitals to establish a scientific epidemic prevention and control system, and become a long-term effect mechanism. METHODS: Based on the principles of management of three links of infectious diseases "infectious source, transmission route and susceptible population", through strengthening personnel training, health monitoring, disinfection and protection, material allocation and health science popularization, optimizing diagnosis and treatment area and channel, establishing emergency plans and supervision mechanism, strengthening the management of key departments and the application of artificial intelligence, combined with the actual situation of the hospital, the general hospital formulated scientific and effective prevention and control strategies, payed attention to detail, and ensured the implementation of prevention and control measures. RESULTS: The hospital diagnosis and treatment activities were carried out in an orderly manner, the prevention and control measures were effective and feasible, the awareness of prevention and control of infectious diseases of doctors and patients was significantly enhanced, and the awareness rate of prevention and control knowledge reached 100.00%. The compliance of hand hygiene of medical personnel was improved, and the standards for wearing and removing of protective equipment and disinfection and sterilization were reasonable. The hospital staff, outpatient emergency and inpatients were not infected with COVID-19. CONCLUSION: The establishment and application of a scientific hospital infection prevention and control system can effectively control the spread and infection of novel coronavirus in general hospitals.

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