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1.
Toxins ; 14(4):N.PAG-N.PAG, 2022.
Article in English | Academic Search Complete | ID: covidwho-1834904

ABSTRACT

Animal feed (including forage and silage) can be contaminated with mycotoxins. Here, 200 maize silage samples from around China were collected in 2019 and analyzed for regulated mycotoxins, masked mycotoxins (deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, and deoxynivalenol-3-glucoside), and emerging mycotoxins (beauvericin, enniatins, moniliformin, and alternariol). Deoxynivalenol and zearalenone were detected in 99.5% and 79.5% of the samples, respectively. Other regulated mycotoxins were detected in fewer samples. The highest deoxynivalenol and zearalenone concentrations were 3600 and 830 μg/kg, respectively. The most commonly detected masked mycotoxin was 15-acetyldeoxynivalenol, which was detected in 68.5% of the samples and had median and maximum concentrations of 61.3 and 410 μg/kg, respectively. The emerging mycotoxins beauvericin, alternariol, enniatin A, enniatin B1, and moniliformin were detected in 99.5%, 85%, 80.5%, 72.5%, and 44.5%, respectively, of the samples but at low concentrations (medians <25 μg/kg). The samples tended to contain multiple mycotoxins, e.g., the correlation coefficients for the relationships between the concentrations of beauvericin and deoxynivalenol, deoxynivalenol and zearalenone, and zearalenone and beauvericin were 1.0, 0.995, and 0.995, respectively. The results indicated that there needs to be more awareness of the presence of one or more masked and emerging mycotoxins in maize silage in China. [ FROM AUTHOR] Copyright of Toxins is the property of MDPI 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.)

2.
Journal of Business Research ; 2022.
Article in English | ScienceDirect | ID: covidwho-1819521

ABSTRACT

Co-location has been a relevant topic in the international business literature, yet the extant literature focuses on the co-location of research and development (R&D) and production activities and overlooks marketing value activities. Marketing innovation is an agile and effective way to respond to crises such as the COVID-19 pandemic, and many manufacturers in global value chains aim to upgrade functionally following the trajectory of the OEM-ODM-OBM. Thus, this study proposes the co-location of marketing activities as a flexible and organizational learning strategy for manufacturing upgrades, and explores the antecedents of marketing co-location in foreign direct investment (FDI) decisions. The proposed research framework was examined using survey data from 343 Taiwanese manufacturing firms in China, which were drawn from a database compiled by Taiwan’s Ministry of Economic Affairs in 2020. The results show that the breadth of international experience, linkage to R&D, marketing as a primary knowledge source in the host country, upgrading for local demands, and new product development for global supply are all positively associated with the co-location of marketing and production functions. Additionally, it was found that there was a negative association between FDIs that had been impacted by COVID-19 and marketing co-location. The findings provide valuable theoretical, practical, and strategic insights into how firms should manage their global value chains with respect to marketing co-location in case of another crisis.

3.
BMC Pulm Med ; 22(1): 52, 2022 Feb 05.
Article in English | MEDLINE | ID: covidwho-1690928

ABSTRACT

COVID-19 has inflicted the world for over two years. The recent mutant virus strains pose greater challenges to disease prevention and treatment. COVID-19 can cause acute respiratory distress syndrome (ARDS) and extrapulmonary injury. Dynamic monitoring of each patient's condition is necessary to timely tailor treatments, improve prognosis and reduce mortality. Point-of-care ultrasound (POCUS) is broadly used in patients with ARDS. POCUS is recommended to be performed regularly in COVID-19 patients for respiratory failure management. In this review, we summarized the ultrasound characteristics of COVID-19 patients, mainly focusing on lung ultrasound and echocardiography. Furthermore, we also provided the experience of using POCUS to manage COVID-19-related ARDS.


Subject(s)
COVID-19/diagnostic imaging , Echocardiography , Lung/diagnostic imaging , Point-of-Care Testing , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Therapy/methods , COVID-19/therapy , Humans , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324313

ABSTRACT

HBV infection is a major global health burden that needs novel immunotherapeutic approaches. Herein, we show that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a novel drug target for HBV infection. We reveal the new target with highly selective probes of PAC5, a natural sesquiterpene derivative. PAC5 show potent anti-HBV activity in vivo and in vitro. Further studies on its mode of action indicate that PAC5 binds to the residue Asp49 and a deep groove in the RNA recognition motif1 (RRM1) region of hnRNPA2B1. PAC5-bound hnRNPA2B1 is activated, dimerized, and translocated to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to the production of type I interferons (IFNs). Furthermore, PAC5 also suppresses other viral replications, such as SARS-CoV-2 and vesicular stomatitis virus (VSV). Our results indicate that PAC5 is the first small molecule agonist of hnRNPA2B1, a drug target potentially valid for broad-spectrum viral infections, providing a novel strategy for viral immunotherapy.

5.
JACS Au ; 1(12): 2315-2327, 2021 Dec 27.
Article in English | MEDLINE | ID: covidwho-1605422

ABSTRACT

For using targeted covalent inhibitors (TCIs) as anticancer and antiviral drugs, we establish that the model compounds PCMPS (p-chloromercuriphenyl sulfate) and PCMB (p-chloromercuribenzoate) are inhibitors of the DEDDh family of exonucleases. The underlying mechanism is analyzed by X-ray crystallography, activity/nucleic acid-binding assays, and all-atom molecular dynamics (MD) simulations. The first TCI-complexed structures of a DEDDh enzyme, the Lassa fever virus NP exonuclease (NPexo), are resolved to elucidate that the Cys409 binding site is away from the active site and the RNA-binding lid. The NPexo C409A structures indicate Cys461 as the alternative distal site for obstructing the equally active mutant. All-atom MD simulations of the wild type and mutant NPexos in explicit solvent uncover an allosteric inhibition mechanism that the local perturbation induced by PCMPS sulfonate propagates to impact the RNA-binding lid conformation. Binding assay studies confirm that PCMPS does affect the RNA binding of NPexo. The predicted relative potency between PCMPS and PCMB is also in line with experiments. The structural data and inhibition mechanism established in this work provide an important molecular basis for the drug development of TCIs.

6.
Front Med (Lausanne) ; 8: 753659, 2021.
Article in English | MEDLINE | ID: covidwho-1556286

ABSTRACT

Background: Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs), but risk factors for COVID-19-associated IPA (CAPA) have not been fully characterized. The aim of the current study was to identify factors associated with CAPA, and assess long-term mortality. Methods: A retrospective cohort study of adult COVID-19 patients admitted to ICUs from six hospitals was conducted in Hubei, China. CAPA was diagnosed via composite clinical criteria. Demographic information, clinical variables, and 180-day outcomes after the diagnosis of CAPA were analyzed. Results: Of 335 critically ill patients with COVID-19, 78 (23.3%) developed CAPA within a median of 20.5 days (range 13.0-42.0 days) after symptom onset. Compared to those without CAPA, CAPA patients were more likely to have thrombocytopenia (50 vs. 19.5%, p < 0.001) and secondary bacterial infection prior to being diagnosed with CAPA (15.4 vs. 6.2%, p = 0.013), and to receive vasopressors (37.2 vs. 8.6%, p < 0.001), higher steroid dosages (53.9 vs. 34.2%, p = 0.002), renal replacement therapy (37.2 vs. 13.6%, p < 0.001), and invasive mechanical ventilation (57.7 vs. 35.8%, p < 0.001). In multivariate analysis incorporating hazard ratios (HRs) and confidence intervals (CIs), thrombocytopenia (HR 1.98, 95% CI 1.16-3.37, p = 0.012), vasopressor use (HR 3.57, 95% CI 1.80-7.06, p < 0.001), and methylprednisolone use at a daily dose ≥ 40 mg (HR 1.69, 95% CI 1.02-2.79, p = 1.02-2.79) before CAPA diagnosis were independently associated with CAPA. Patients with CAPA had longer median ICU stays (17 days vs. 12 days, p = 0.007), and higher 180-day mortality (65.4 vs. 33.5%, p < 0.001) than those without CAPA. Conclusions: Thrombocytopenia, vasopressor use, and corticosteroid treatment were significantly associated with increased risk of incident IPA in COVID-19 patients admitted to ICUs. The occurrence of CAPA may increase the likelihood of long-term COVID-19 mortality.

7.
Int J Environ Res Public Health ; 18(23)2021 11 26.
Article in English | MEDLINE | ID: covidwho-1542527

ABSTRACT

A record outbreak of community-spread COVID-19 started on 10 May 2021, in Taiwan. In response to the COVID-19 pandemic, care facilities have adopted various protocols using instant communication technology (ICT) to provide remote yet timely healthcare while ensuring staff safety. The challenges of patient evaluation in the emergency department (ED) using ICT are seldom discussed in the literature. The objective of this study was to investigate the factors influencing the utility of ICT for patient assessment in emergency settings during the pandemic. The patient flow protocol and the ED layout were modified and regionalized into different areas according to the patient's risk of COVID-19 infection. Nine iPads were stationed in different zones to aid in virtual patient assessment and communication between medical personnel. A focus group study was performed to assess and analyze the utility of the ICT module in the ED. Eight emergency physicians participated in the study. Of them, four (50%) had been directly involved in the development of the ICT module in the study hospital. Three main themes that influenced the application of the ICT module were identified: setting, hardware, and software. The setting theme included six factors: patient evaluation, subspecialty consultation, patient privacy and comfortableness, sanitation, cost, and patient acceptability. The hardware theme included six factors: internet connection, power, quality of image and voice, public or personal mode, portable or fixed mode, and maintenance. The software theme included six factors: platform choices, security, ICT accounts, interview modes, video/voice recording, and time limitation. Future studies should focus on quantifying module feasibility, user satisfaction, and protocol adjustment for different settings.


Subject(s)
COVID-19 , Pandemics , Communication , Emergency Service, Hospital , Focus Groups , Humans , SARS-CoV-2 , Technology
8.
Front Med (Lausanne) ; 8: 694754, 2021.
Article in English | MEDLINE | ID: covidwho-1485067

ABSTRACT

To investigate the characteristics of SARS-CoV-2 pneumonia and evaluate whether CT scans, especially at a certain CT level, could be used to predict the severity of SARS-CoV-2 pneumonia. In total 118 confirmed patients had been enrolled. All data including epidemiological, clinical characteristics, laboratory results, and images were collected and analyzed when they were administrated for the first time. All patients were divided into two groups. There were 106 severe/critical patients and 12 common ones. A total of 38 of the patients were women. The mean age was 50.5 ± 11.5 years. Overall, 80 patients had a history of exposure. The median time from onset of symptoms to administration was 8.0 days. The main symptoms included fever, cough, anorexia, fatigue, myalgia, headaches, and chills. Lymphocytes and platelets decreased and lactate dehydrogenase increased with increased diseased severity (P < 0.05). Calcium and chloride ions were decreased more significantly in severe/critical patients than in common ones (P < 0.05). The main comorbidities were diabetes, chronic cardiovascular disease, and chronic pulmonary disease, which occurred in 47 patients. In all 69 patients had respiratory failure, which is the most common SARS-CoV-2 complication, and liver dysfunction presented in 37 patients. Nine patients received mechanical ventilation therapy. One patient received continuous blood purification and extracorporeal membrane oxygenation (EMCO) treatments. The average stay was 18.1 ± 10.8 days. Four patients died. The median of the radiographic score was four in common, and five in the severe/critical illness, which was a significant difference between the two groups. The radiographic score was in negative correlation with OI (ρ = -0.467, P < 0.01). The OI in severe/critically ill cases decreased significantly as the disease progressed, which was related to the lesion area in the left lung and right lungs (ρ = 0.688, R = 0.733). OI, the lesion area in the left lung and right lungs, lymphocytes, etc. were associated with different degrees of SARS-CoV-2 pneumonia (P < 0.05). The lesion area in both lungs were possible predictive factors for severe/critical cases. Patients with SARS-CoV-2 pneumonia showed obvious clinical manifestations and laboratory result changes. Combining clinical features and the quantity of the lesion area in the fourth level of CT could effectively predict severe/critical SARS-CoV-2 cases.

9.
Preprint in English | medRxiv | ID: ppmedrxiv-21265691

ABSTRACT

BackgroundDuring the COVID-19 outbreak in Taiwan between May 11 and June 20, 2021, the observed fatality rate (FR) was 5.3%, higher than the global average at 2.1%. The high number of reported deaths suggests that hospital capacity was insufficient. However, many unexplained deaths were subsequently identified as cases, indicating that there were a few undetected cases, hence resulting in a higher estimate of FR. Estimating the number of total infected cases or knowing how to reduce the undetected cases can allow an accurate estimation of the fatality rate (FR) and effective reproduction number (Rt). MethodsAfter adjusting for reporting delays, we estimated the number of undetected cases using reported deaths that were and were not previously detected. The daily FR and Rt were calculated using the number of total cases (i.e. including undetected cases). A logistic regression model was developed to predict the detection ratio among deaths using selected predictors from daily testing and tracing data. ResultsThe estimated true daily case number at the peak of the outbreak on May 22 was 897, which was 24.3% higher than the reported number, but the difference became less than 4% on June 9 and afterward. After taking account of undetected cases, our estimated mean FR (4.7%) was still high but the daily rate showed a large decrease from 6.5% on May 19 to 2.8% on June 6. Rt reached a maximum value of 6.4 on May 11, compared to 6.0 estimated using the reported case number. The decreasing proportion of undetected cases was associated with the increases in the ratio of the number of tests conducted to reported cases, and the proportion of cases that are contact-traced before symptom onset. ConclusionsIncreasing testing capacity and tracing efficiency can lead to a reduction of hidden cases and hence improvement in epidemiological parameter estimation.

10.
Preprint in English | medRxiv | ID: ppmedrxiv-21264017

ABSTRACT

BackgroundAlthough associations between key weather indicators (i.e. temperature and humidity) and COVID-19 mortality has been reported, the relationship between these exposures among different timing in early infection stages (from virus exposure up to a few days after symptom onset) and the probability of death after infection (also called case fatality rate, CFR) has yet to be determined. MethodsWe estimated the instantaneous CFR of eight European countries using Bayesian inference in conjunction with stochastic transmission models, taking account of delays in reporting the number of newly confirmed cases and deaths. The exposure-lag-response associations between fatality rate and weather conditions to which patients were exposed at different timing were obtained using distributed lag nonlinear models coupled with mixed-effect models. ResultsOur results showed that the Odds Ratio (OR) of death is negatively associated with the temperature, with two maxima (OR=1.29 (95% CI: 1.23, 1.35) at -0.1{degrees}C; OR=1.12 (95% CI: 1.08, 1.16) at 0.1{degrees}C) occurred at the time of virus exposure and after symptom onset. Two minima (OR=0.81 (95% CI: 0.71, 0.92) at 23.2{degrees}C; OR=0.71 (95% CI: 0.63, 0.80) at 21.7{degrees}C) also occurred at these two distinct periods correspondingly. Low humidity (below 50%) during the early stages and high humidity (approximately 89%) after symptom onset were related to the lower fatality. ConclusionEnvironmental conditions may affect not only the initial viral load when exposure to viruses but also individuals immunity response around symptom onset. Warmer temperatures and higher humidity after symptom onset were related to the lower fatality. HighlightsO_LITemperature and humidity conditions that patients were exposed to during their early infection stages were associated with COVID-19 case fatality rate. C_LIO_LIWarmer temperatures (> 20{degrees}C) at infection time or after symptom onset, but not during the incubation period, were associated with lower death risk. Low relative humidity (< 50%) during the early stages and high relative humidity (> 85%) after symptom onset were related to higher death risk. C_LIO_LICreating optimal indoor conditions for cases who are under quarantine/isolation may reduce their risk of death. C_LI

11.
Front Med (Lausanne) ; 7: 611460, 2020.
Article in English | MEDLINE | ID: covidwho-1389196

ABSTRACT

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. Results: The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO2 of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

12.
Applied Sciences ; 11(16):7245, 2021.
Article in English | MDPI | ID: covidwho-1348599

ABSTRACT

The COVID-19 pandemic has made it necessary for medical personnel to protect themselves from aerosol-producing procedures, especially during airway management. The tracheal intubation process has a significant risk based on the spreading of aerosol, especially when the medical service provider is very close to the airway of the patient. We have developed a novel conservation tent that provides a barrier for healthcare professionals and patients. Through a simulation study, the relationship between the use of the protection tent during intubation and the contamination of medical personnel before and after the movement of the protection tent was explored. A series of experiments in this article provide a theoretical basis for the verification of spray morphology during gas curing and droplet intubation. This inexpensive and simple method for using transparent cloth in the intubation of patients with unknown COVID-19 status can be applied by frontline medical personnel as an additional precautionary measure.

13.
Preprint in English | bioRxiv | ID: ppbiorxiv-448958

ABSTRACT

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

14.
Preprint in English | medRxiv | ID: ppmedrxiv-21258672

ABSTRACT

With the COVID-19 vaccination widely implemented in most countries, propelled by the need to revive the tourism economy, there is a growing prospect for relieving the social distancing regulation and reopening borders in tourism-oriented countries and regions. The need incentivizes stakeholders to develop border control strategies that fully evaluate health risks if mandatory quarantines are lifted. In this study, we have employed a computational approach to investigate the contact tracing integrated policy in different border reopening scenarios in Hong Kong, China. Built on a modified SEIR epidemic model with a 30% vaccination coverage, the results suggest that scenarios with digital contact tracing and quick isolation intervention can reduce the infectious population by 92.11% compared to those without contact tracing. By further restricting the inbound population with a 10,000 daily quota and applying moderate-to-strong community non-pharmacological interventions (NPIs), the average daily confirmed cases in the forecast period of 60 days can be well controlled at around 9 per day (95% CI: 7-12). Two main policy recommendations are drawn from the study. First, digital contact tracing would be an effective countermeasure for reducing local virus spread, especially when it is applied along with a moderate level of vaccination coverage. Second, implementing a daily quota on inbound travelers and restrictive community NPIs would further keep the local infection under control. This study offers scientific evidence and prospective guidance for developing and instituting plans to lift mandatory border control policies in preparing for the global economic recovery.

15.
Journal of Database Management ; 32(2):67, 2021.
Article in English | ProQuest Central | ID: covidwho-1209920

ABSTRACT

IS/IT plays an important role in our everyday life, especially in today's Internet era. This article discusses the roles of IS/IT in providing services and support on information gathering, analysis, and management during major public emergencies and pandemic crises such as the battle against the new coronavirus. The five selected papers in this special issue introduce advanced methods on data collection and social media user analysis to deal with the challenges brought by the COVID-19 pandemic. This paper also presents future research directions on the use of IS/IT in emergency and pandemic management such as IS control and governance, intelligent health care, enhancing people's lives and mental health, and knowledge management.

16.
Nature ; 593(7859): 418-423, 2021 05.
Article in English | MEDLINE | ID: covidwho-1137788

ABSTRACT

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.


Subject(s)
Antiviral Agents/pharmacology , Clofazimine/pharmacology , Coronavirus/classification , Coronavirus/drug effects , SARS-CoV-2/drug effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , Biological Availability , Cell Fusion , Cell Line , Clofazimine/pharmacokinetics , Clofazimine/therapeutic use , Coronavirus/growth & development , Coronavirus/pathogenicity , Cricetinae , DNA Helicases/antagonists & inhibitors , Drug Synergism , Female , Humans , Life Cycle Stages/drug effects , Male , Mesocricetus , Pre-Exposure Prophylaxis , SARS-CoV-2/growth & development , Species Specificity , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Transcription, Genetic/drug effects , Transcription, Genetic/genetics
17.
Natl Sci Rev ; 7(7): 1157-1168, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1114858

ABSTRACT

The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.

18.
Eur Heart J Acute Cardiovasc Care ; 10(1): 6-15, 2021 Mar 05.
Article in English | MEDLINE | ID: covidwho-1096511

ABSTRACT

AIMS: To investigate the association between levels of highly sensitive troponin I (hs-troponin I) and mortality in novel coronavirus disease 2019 (COVID-19) patients with cardiac injury. METHODS AND RESULTS: We retrospectively reviewed the medical records of all COVID-19 patients with increased levels of hs-troponin I from two hospitals in Wuhan, China. Demographic information, laboratory test results, cardiac ultrasonographic findings, and electrocardiograms were collected, and their predictive value on in-hospital mortality was explored using multivariable logistic regression. Of 1500 patients screened, 242 COVID-19 patients were enrolled in our study. Their median age was 68 years, and (48.8%) had underlying cardiovascular diseases. One hundred and seventy-six (72.7%) patients died during hospitalization. Multivariable logistic regression showed that C-reactive protein (>75.5 mg/L), D-dimer (>1.5 µg/mL), and acute respiratory distress syndrome were risk factors of mortality, and the peak hs-troponin I levels (>259.4 pg/mL) instead of the hs-troponin I levels at admission was predictor of death. The area under the receiver operating characteristic curve of the peak levels of hs-troponin I for predicting in-hospital mortality was 0.79 (95% confidence interval, 0.73-0.86; sensitivity, 0.80; specificity, 0.72; P < 0.0001). CONCLUSION: Our results demonstrated that the risk of in-hospital death among COVID-19 patients with cardiac injury can be predicted by the peak levels of hs-troponin I during hospitalization and was significantly associated with oxygen supply-demand mismatch, inflammation, and coagulation.


Subject(s)
COVID-19/blood , COVID-19/mortality , Heart Diseases/blood , Heart Diseases/mortality , Hospital Mortality , Troponin I/blood , Aged , COVID-19/complications , Female , Heart Diseases/etiology , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity
19.
J Biol Chem ; 296: 100435, 2021.
Article in English | MEDLINE | ID: covidwho-1087033

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents a global threat, and the interaction between the virus and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. However, the mechanisms underpinning ACE2-mediated viral entry across species remains unclear. Using infection assay, we evaluated SARS-CoV-2 entry mediated by ACE2 of 11 different animal species. We discovered that ACE2 of Rhinolophus sinicus (Chinese rufous horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (wild pig), Capra hircus (goat), and Manis javanica (Malayan pangolin) facilitated SARS-CoV-2 entry into nonsusceptible cells. Moreover, ACE2 of the pangolin also mediated SARS-CoV-2 entry, adding credence to the hypothesis that SARS-CoV-2 may have originated from pangolins. However, the ACE2 proteins of Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (red junglefowl), Notechis scutatus (mainland tiger snake), or Mus musculus (house mouse) did not facilitate SARS-CoV-2 entry. In addition, a natural isoform of the ACE2 protein of Macaca mulatta (rhesus monkey) with the Y217N mutation was resistant to SARS-CoV-2 infection, highlighting the possible impact of this ACE2 mutation on SARS-CoV-2 studies in rhesus monkeys. We further demonstrated that the Y217 residue of ACE2 is a critical determinant for the ability of ACE2 to mediate SARS-CoV-2 entry. Overall, these results clarify that SARS-CoV-2 can use the ACE2 receptors of multiple animal species and show that tracking the natural reservoirs and intermediate hosts of SARS-CoV-2 is complex.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/epidemiology , COVID-19/transmission , Pandemics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/immunology , Animals , COVID-19/diagnosis , COVID-19/immunology , Cats , Chickens/virology , Chiroptera/virology , Dogs , Elapidae/virology , Eutheria/virology , Gene Expression , Goats/virology , HEK293 Cells , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate , Macaca mulatta/virology , Mice , Models, Molecular , Mutation , Protein Binding , Protein Structure, Secondary , Recombinant Proteins/genetics , Recombinant Proteins/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Species Specificity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Swine/virology , Virus Internalization
20.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-5350

ABSTRACT

A review. Abstract In Dec. 2019, the outbreak of corona virus disease-19 (COVID-19) occurred in Wuhan, China. Cytokine storm (inflammatory factor storm) was suggested to be involved in the sudden deterioration of some COVID-19 infectors. However, no medicine was specific to the treatment of cytokine storm so far. Tocilizumab is IL-6 receptor antagonist, which probably blocks cytokine storm to prevent COVID-19 from serious illness. However, with limited evidence, clinicians are facing many problems while using this medication in clin. practice, such as absence of detailed instruction in general and special populations, unclear rationale behind recommendations, etc. In this paper, basic information, research status in domestic and international of tocilizumab, drug interaction, and adverse reaction are summarized in order to provide reference for clin. medication.

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