Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 35
Filter
Add filters

Year range
1.
BMJ Open ; 11(11): e056636, 2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1533053

ABSTRACT

OBJECTIVES: Importations of novel variants of concern (VOC), particularly B.1.617.2, have become the impetus behind recent outbreaks of SARS-CoV-2. Concerns around the impact on vaccine effectiveness, transmissibility and severity are now driving the public health response to these variants. This paper analyses the patterns of growth in hospitalisations and confirmed cases for novel VOCs by age groups, geography and ethnicity in the context of changing behaviour, non-pharmaceutical interventions (NPIs) and the UK vaccination programme. We seek to highlight where strategies have been effective and periods that have facilitated the establishment of new variants. DESIGN: We have algorithmically linked the most complete testing and hospitalisation data in England to create a data set of confirmed infections and hospitalisations by SARS-CoV-2 genomic variant. We have used these linked data sets to analyse temporal, geographic and demographic distinctions. SETTING AND PARTICIPANTS: The setting is England from October 2020 to July 2021. Participants included all COVID-19 tests that included RT-PCR CT gene target data or underwent sequencing and hospitalisations that could be linked to these tests. METHODS: To calculate the instantaneous growth rate for VOCs we have developed a generalised additive model fit to multiple splines and varying day of the week effects. We have further modelled the instantaneous reproduction number Rt for the B.1.1.7 and B.1.617.2 variants and included a doubly interval censored model to temporally adjust the confirmed variant cases. RESULTS: We observed a clear replacement of the predominant B.1.1.7 by the B.1.617.2 variant without observing sustained exponential growth in other novel variants. Modelled exponential growth of RT PCR gene target triple-positive cases was initially detected in the youngest age groups, although we now observe across all ages a very small doubling time of 10.7 (95% CI 9.1 to 13.2) days and 8 (95% CI 6.9 to 9.1) days for cases and hospitalisations, respectively. We observe that growth in RT PCR gene target triple-positive cases was first detected in the Indian ethnicity group in late February, with a peak of 0.06 (95% CI 0.07 to 0.05) in the instantaneous growth rate, but is now maintained by the white ethnicity groups, observing a doubling time of 6.8 (95% CI 4.9 to 11) days. Rt analysis indicates a reproduction number advantage of 0.45 for B.1.617.2 relative to B.1.1.7, with the Rt value peaking at 1.85 for B.1.617.2. CONCLUSIONS: Our results illustrate a clear transmission advantage for the B.1.617.2 variant and the growth in hospitalisations illustrates that this variant is able to maintain exponential growth within age groups that are largely doubly vaccinated. There are concerning signs of intermittent growth in the B.1.351 variant, reaching a 28-day doubling time peak in March 2021, although this variant is presently not showing any evidence of a transmission advantage over B.1.617.2. Step 1b of the UK national lockdown easing was sufficient to precipitate exponential growth in B.1.617.2 cases for most regions and younger adult age groups. The final stages of NPI easing appeared to have a negligible impact on the growth of B.1.617.2 with every region experiencing sustained exponential growth from step 2. Nonetheless, early targeted local NPIs appeared to markedly reduced growth of B.1.617.2. Later localised interventions, at a time of higher prevalence and greater geographic dispersion of this variant, appeared to have a negligible impact on growth.

2.
Preprint in English | EuropePMC | ID: ppcovidwho-291204

ABSTRACT

A novel coronavirus (2019-nCoV) that is initially found to trigger human severe respiratory illness in Wuhan City of China, 2019, has been recognized as a public health emergency of international concern. In the past two months, this deadly agent has caused 77,785 cases with 2,666 deaths via rapid person-to-person transmission and reached at least 25 countries. However, its evolutionary origin is poorly understood. Here we show integrative evidence that 2019-nCoV is a possible progenitor for SARS-CoV with bat origin. Our finding underscores the importance of tracing origin in the efficient monitoring, and effectively preventing the interspecies transmission of such emerging/re-emerging coronaviruses.

3.
J Trauma Nurs ; 28(5): 298-303, 2021.
Article in English | MEDLINE | ID: covidwho-1455396

ABSTRACT

BACKGROUND: The high mortality rate of comatose patients with traumatic brain injury is a prominent public health issue that negatively impacts patients and their families. Objective, reliable tools are needed to guide treatment decisions and prioritize resources. OBJECTIVE: This study aimed to evaluate the prognostic value of the bispectral index (BIS) in comatose patients with severe brain injury. METHODS: This was a retrospective cohort study of 84 patients with severe brain injury and Glasgow Coma Scale (GCS) scores of 8 and less treated from January 2015 to June 2017. Sedatives were withheld at least 24 hr before BIS scoring. The BIS value, GCS scores, and Full Outline of UnResponsiveness (FOUR) were monitored hourly for 48 hr. Based on the Glasgow Outcome Scale (GOS) score, the patients were divided into poor (GOS score: 1-2) and good prognosis groups (GOS score: 3-5). The correlation between BIS and prognosis was analyzed by logistic regression, and the receiver operating characteristic curves were plotted. RESULTS: The mean (SD) of the BIS value: 54.63 (11.76), p = .000; and GCS score: 5.76 (1.87), p = .000, were higher in the good prognosis group than in the poor prognosis group. Lower BIS values and GCS scores were correlated with poorer prognosis. Based on the area under the curve of receiver operating characteristic curves, the optimal diagnostic cutoff value of the BIS was 43.6, and the associated sensitivity and specificity were 85.4% and 74.4%, respectively. CONCLUSION: Taken together, our study indicates that BIS had good predictive value on prognosis. These findings suggested that BIS could be used to evaluate the severity and prognosis of severe brain injury.


Subject(s)
Brain Injuries , Coma , Coma/diagnosis , Electroencephalography , Glasgow Coma Scale , Humans , Prognosis , Retrospective Studies
4.
J Agric Food Chem ; 69(41): 12197-12208, 2021 Oct 20.
Article in English | MEDLINE | ID: covidwho-1442683

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (Mpro) inhibitors are considered as potential treatments for coronavirus disease 2019, and dietary polyphenols show promise in SARS-CoV-2 Mpro inhibition based on in silico studies. In the present study, we utilize a combination of biochemical-, surface plasmon resonance-, and docking-based assays to evaluate the inhibition and binding affinities of a series of tannins and their gut microbial metabolites on SARS-CoV-2 Mpro. The tested compounds (2-50 µM) were hydrolyzable tannins, including ellagitannins (punicalagin and ellagic acid) and gallotannins (tannic acid, pentagalloyl glucose, ginnalin A, and gallic acid), and their gut microbial metabolites, urolithins and pyrogallol, respectively. They inhibited SARS-CoV-2 Mpro (by 6.6-100.0% at 50 µM) and bound directly to the Mpro protein (with dissociation constants from 1.1 × 10-6 to 5.3 × 10-5 M). This study sheds light on the inhibitory effects of tannins and their metabolites on SARS-CoV-2 Mpro.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Humans , Hydrolyzable Tannins , Molecular Docking Simulation , Peptide Hydrolases , Protease Inhibitors , SARS-CoV-2 , Surface Plasmon Resonance
5.
FASEB J ; 35(9): e21870, 2021 09.
Article in English | MEDLINE | ID: covidwho-1373669

ABSTRACT

COVID-19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing-Fei-Pai-Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune-related molecules were the targets of the active components of QFPDD, which propelled us to examine the effects of the decoction on inflammation. We found in the present study that QFPDD effectively alleviated dextran sulfate sodium-induced intestinal inflammation in mice. It inhibited the production of pro-inflammatory cytokines IL-6 and TNFα, and promoted the expression of anti-inflammatory cytokine IL-10 by macrophagic cells. Further investigations found that QFPDD and one of its active components wogonoside markedly reduced LPS-stimulated phosphorylation of transcription factor ATF2, an important regulator of multiple cytokines expression. Our data revealed that both QFPDD and wogonoside decreased the half-life of ATF2 and promoted its proteasomal degradation. Of note, QFPDD and wogonoside down-regulated deubiquitinating enzyme USP14 along with inducing ATF2 degradation. Inhibition of USP14 with the small molecular inhibitor IU1 also led to the decrease of ATF2 in the cells, indicating that QFPDD and wogonoside may act through regulating USP14 to promote ATF2 degradation. To further assess the importance of ubiquitination in regulating ATF2, we generated mice that were intestinal-specific KLHL5 deficiency, a CUL3-interacting protein participating in substrate recognition of E3s. In these mice, QFPDD mitigated inflammatory reaction in the spleen, but not intestinal inflammation, suggesting CUL3-KLHL5 may function as an E3 for ATF2 degradation.


Subject(s)
Activating Transcription Factor 2/metabolism , Down-Regulation/drug effects , Drugs, Chinese Herbal/pharmacology , Flavanones/pharmacology , Glucosides/pharmacology , Inflammation/drug therapy , Proteolysis/drug effects , Ubiquitin Thiolesterase/deficiency , Animals , Cell Line , Colitis/chemically induced , Colitis/drug therapy , Cullin Proteins/metabolism , Cytokines/metabolism , Dextran Sulfate/pharmacology , Dextran Sulfate/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Flavanones/therapeutic use , Glucosides/therapeutic use , Inflammation/chemically induced , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Phosphorylation/drug effects , Proteasome Endopeptidase Complex/drug effects , Proteasome Endopeptidase Complex/metabolism , Pyrroles/pharmacology , Pyrrolidines/pharmacology , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitination
7.
J Pharm Policy Pract ; 14(1): 66, 2021 Aug 06.
Article in English | MEDLINE | ID: covidwho-1344127

ABSTRACT

BACKGROUND: Coronavirus disease (COVID-19) pandemic posed a critical threat to public health in the past year and has not been fully controlled so far. The nature of front-line young hospital pharmacists' occupation puts them at an increased risk of contracting any contagious disease, including COVID-19. Recent survey indicated that hospital pharmacists in China are depressive, hostile amid the pandemic. AIM: The present investigation aims to understand the job stress among young hospital pharmacists during the outbreak of COVID-19 and to provide basic information for pharmacy managers to help young fellows to cope with job stress. METHOD: This study is adopting pharmacist job stress questionnaire as the key instrument of data collection through WJX App in mobile phone. Demographic information, career prospects and stress management proposals were obtained synchronously. Quantitative data were processed with SPSS. Significant differences were examined using analysis of variance and Chi-square analysis. RESULT: About 60% of 289 questionnaire respondents complained of job stress (178 respondents). According to the narrative description of the data, young pharmacists' gender, education background, hospital grade, and specific work post had no significant effect on job stress difference. However, young pharmacists in different age-groups and professional titles showed different job stress. Pharmacists at the age of 31-35 complained more stress than the others. Pharmacists with high professional title (deputy chief pharmacist) complained more stress than the others. About 65% of 289 respondents had long-term plan for their practice, although 61% of young pharmacists felt troubled or worried with their future. As for stress management proposal, almost all young pharmacists hoped to improve their professional identity via raising their wages. CONCLUSION: More than half of young pharmacists suffer from job stress amidst the COVID-19 pandemic in China, and various intervention measures should be taken to relieve the stress and finally improve their social identity.

8.
BMC Emerg Med ; 21(1): 88, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1327808

ABSTRACT

BACKGROUND: To present the new trends in epidemiology of road traffic injuries (RTIs) during the Coronavirus disease 2019 (COVID-19) pandemic in Suzhou. METHODS: Pre-hospital records of RTIs from January to May in 2020 and the same period in 2019 were obtained from the database of Suzhou pre-hospital emergency center, Jiangsu, China. Data were extracted for analysis, including demographic characteristics, pre-hospital vital signs, transport, shock index, consciousness, pre-hospital death. A retrospective study comparing epidemiological characteristics of RTIs in Suzhou during the 5-month period in 2020 to the parallel period in 2019 was performed. RESULTS: A total of 7288 RTIs in 2020 and 8869 in 2019 met inclusion criteria. The overall volume of RTIs has statistical difference between the 2 years (p < 0.001), with fewer RTIs in 2020 compared with 2019. Electric bicycle related RTIs increased during the pandemic (2641, 36.24% vs 2380, 26.84%, p < 0.001), with a higher incidence of RTIs with disorder of consciousness (DOC) (7.22% vs 6.13%, p = 0.006). CONCLUSIONS: Under the impact of COVID-19, the total number of RTIs in Suzhou from January to May 2020 decreased. This observation was coupled with a rise in electric bicycle related injuries and an increase in the incidence of RTIs with DOC.


Subject(s)
Accidents, Traffic/statistics & numerical data , Bicycling/statistics & numerical data , COVID-19/epidemiology , Wounds and Injuries/epidemiology , China , Humans , Incidence , Motorcycles/statistics & numerical data , Retrospective Studies , Risk Factors
9.
World J Clin Cases ; 9(19): 5266-5269, 2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1314996

ABSTRACT

BACKGROUND: Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported. CASE SUMMARY: A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d. CONCLUSION: COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.

10.
Exp Ther Med ; 21(2): 115, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1299606

ABSTRACT

Since December 2019, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. At present, confirmed patients are the main source of infection, while a number of studies have indicated that asymptomatic carriers also have the ability to spread the virus. As of September 29, 2020, as the first country to report coronavirus disease 2019 (COVID-19), China has 375 asymptomatic infections according to the National Health Commission of China. Asymptomatic carriers have become the current focus of global epidemic prevention and control efforts. The present review article provides a brief introduction on the clinical characteristics and infectivity of asymptomatic carriers, and makes suggestions for the identification of asymptomatic carriers.

11.
Diseases ; 9(3)2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1288832

ABSTRACT

The newly found SARS-CoV-2 has led to the pandemic of COVID-19, which has caused respiratory distress syndrome and even death worldwide. This has become a global public health crisis. Unfortunately, elders and subjects with comorbidities have high mortality rates. One main feature of COVID-19 is the cytokine storm, which can cause damage in cells and tissues including the kidneys. Here, we reviewed the current literature on renal impairments in patients with COVID-19 and analyzed the possible etiology and mechanisms. In addition, we investigated the potential use of vitamin C for the prevention of renal injury in those patients. It appears that vitamin C could be helpful to improve the outcomes of patients with COVID-19. Lastly, we discussed the possible protective effects of vitamin C on renal functions in COVID-19 patients with existing kidney conditions.

12.
Am J Trop Med Hyg ; 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1270185

ABSTRACT

There is a scarcity of data regarding coronavirus disease 2019 (COVID-19) infection in children from southeast and south Asia. This study aims to identify risk factors for severe COVID-19 disease among children in the region. This is an observational study of children with COVID-19 infection in hospitals contributing data to the Pediatric Acute and Critical Care COVID-19 Registry of Asia. Laboratory-confirmed COVID-19 cases were included in this registry. The primary outcome was severity of COVID-19 infection as defined by the World Health Organization (WHO) (mild, moderate, severe, or critical). Epidemiology, clinical and laboratory features, and outcomes of children with COVID-19 are described. Univariate and multivariable logistic regression models were used to identify risk factors for severe/critical disease. A total of 260 COVID-19 cases from eight hospitals across seven countries (China, Japan, Singapore, Malaysia, Indonesia, India, and Pakistan) were included. The common clinical manifestations were similar across countries: fever (64%), cough (39%), and coryza (23%). Approximately 40% of children were asymptomatic, and overall mortality was 2.3%, with all deaths reported from India and Pakistan. Using the multivariable model, the infant age group, presence of comorbidities, and cough on presentation were associated with severe/critical COVID-19. This epidemiological study of pediatric COVID-19 infection demonstrated similar clinical presentations of COVID-19 in children across Asia. Risk factors for severe disease in children were age younger than 12 months, presence of comorbidities, and cough at presentation. Further studies are needed to determine whether differences in mortality are the result of genetic factors, cultural practices, or environmental exposures.

13.
Sci Rep ; 11(1): 9626, 2021 05 05.
Article in English | MEDLINE | ID: covidwho-1217712

ABSTRACT

Early classification and risk assessment for COVID-19 patients are critical for improving their terminal prognosis, and preventing the patients deteriorate into severe or critical situation. We performed a retrospective study on 222 COVID-19 patients in Wuhan treated between January 23rd and February 28th, 2020. A decision tree algorithm has been established including multiple factor logistic for cluster analyses that were performed to assess the predictive value of presumptive clinical diagnosis and features including characteristic signs and symptoms of COVID-19 patients. Therapeutic efficacy was evaluated by adopting Kaplan-Meier survival curve analysis and cox risk regression. The 222 patients were then clustered into two groups: cluster I (common type) and cluster II (high-risk type). High-risk cases can be judged from their clinical characteristics, including: age > 50 years, chest CT images with multiple ground glass or wetting shadows, etc. Based on the classification analysis and risk factor analysis, a decision tree algorithm and management flow chart were established, which can help well recognize individuals who needs hospitalization and improve the clinical prognosis of the COVID-19 patients. Our risk factor analysis and management process suggestions are useful for improving the overall clinical prognosis and optimize the utilization of public health resources during treatment of COVID-19 patients.


Subject(s)
COVID-19/drug therapy , Aged , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/etiology , COVID-19/therapy , China/epidemiology , Cluster Analysis , Comorbidity , Decision Support Systems, Clinical , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Retrospective Studies , Treatment Outcome
14.
Zhongguo Bingdubing Zazhi = Chinese Journal of Viral Diseases ; - (6):445, 2020.
Article in English | ProQuest Central | ID: covidwho-1126081

ABSTRACT

Objective To establish an index system for comprehensive evaluation of public health risks of the coronavirus diseases 2019(COVID-19),and to evaluate the COVID-19 in different counties(districts) of Wenzhou, so as to provide scientific evidence for the implementation of targeted prevention and control measures. Methods Rank-sum ratio(RSR) was used to evaluate 12 quality indicators of 5 categories by brain storming method with data including the incidence of COVID-19 and public health risks of COVID-19 epidemic in Wenzhou during January and February, 2020.The regional public health risks of COVID-19 were ranked according to rank-sum ratio size. Results The top three counties(districts) with most reported cases were Yueqing,Rui′an and Lucheng,accounting for 61.90%(312/504) of the total number in Wenzhou.The ratio of import cases to indigenous cases was 1∶1.39.The top three counties(districts) reported most clustering epidemics were Yueqing,Rui′an and Lucheng,accounting for 62.03%(49/79) of the total number in Wenzhou.About 70.63%(356/504)of the cases were found before the medical visit.The time from onset to first medical visit was 2.39 d, and the time from medical visit to diagnosis was 4.49 d.The average number of close contacts for confirmed cases was 29,and the top three counties(districts)with most reported average number of close contacts were Jingkai(135 cases),Dongtou(59 cases)and Cangnan(50 cases).Among all13 counties(districts),Longgang,Wencheng and Jingkai were at lower level,Yueqing and Lucheng were at higher level,and the other counties(districts)were at the middle level of public health risks of COVID-19. Conclusions RSR method is flexible and simple.It has no specific requirements on samples,and can eliminate the effects of comprehensive assessment indexes of different dimension.It has high value in evaluating public health risks of the COVID-19.The evaluating of public health risks of COVID-19 should be strengthened.Targeted prevention and control measures should be taken to positively prevent the outbreak of COVID-19.

15.
Chinese Journal of Viral Diseases ; 10(6):445-450, 2020.
Article in Chinese | GIM | ID: covidwho-1125311

ABSTRACT

Objective: To establish a new type of coronavirus pneumonia (coronavirusdisease-19, COVID-19) public health risk assessment index system, evaluate the public health risks of COVID-19, and provide a scientific basis for the implementation of targeted prevention and control measures.

16.
Nat Commun ; 12(1): 814, 2021 02 05.
Article in English | MEDLINE | ID: covidwho-1065864

ABSTRACT

On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO2/FiO2 ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted.


Subject(s)
Bevacizumab/therapeutic use , COVID-19/drug therapy , SARS-CoV-2/drug effects , Aged , Angiogenesis Inhibitors/therapeutic use , Body Temperature/drug effects , COVID-19/virology , China , Female , Fever/prevention & control , Humans , Italy , Male , Middle Aged , SARS-CoV-2/physiology , Treatment Outcome
17.
Preprint | SciFinder | ID: ppcovidwho-5255

ABSTRACT

A review. Since Dec. 2019, Wuhan City, Hubei Province has discovered many cases of new coronavirus-infected pneumonia patients. With the spread of the epidemic, such cases have also been found in other regions of China and abroad. As an acute respiratory infectious disease, the disease was included in Category B infectious diseases as stipulated in the Law of the People's Republic of China on the Prevention and Control of Infectious Diseases on Jan. 20, 2020, and is managed as Category A infectious diseases. WHO in 2020 On Jan. 30, it was announced that the new coronavirus epidemic was listed as a public health emergency of international concern. With the progress of the epidemic and the development of etiol. testing, reports of children 's infections are gradually increasing. There are many cases of children 's reports, and there are cases of infant and newborn infections. With the deepening of disease knowledge and the accumulation of experience in diagnosis and treatment, the National Health and Health Commission has now formulated the "New Coronavirus Infection Pneumonia Diagnosis and Treatment Program (Trial Sixth Edition)" [1]. The Pediatric Branch of the Chinese Medical Association is concluding On the basis of confirmed cases of children, the "Diagnosis and Prevention Recommendations for Children's 2019 New Coronavirus Infection (Trial First Version)" [2], recently issued by the International Virus Classification Committee(International Committee on Taxonomy of Viruses, ICTV) officially identified the name of the new coronavirus as severe acute Respiratory syndrome coronavirus type 2 (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). According to the epidemic situation in Chongqing, combined with the characteristics of children's diseases, on the basis of the revision of the "Diagnosis and Treatment Plan for New Coronavirus Infection in Children's Hospital of Chongqing Medical University (First Edition)", the "New Coronavirus for Children in Children's Hospital of Chongqing Medical University" was formulated Infection diagnosis and treatment plan (trial second edition) ".

18.
Front Pharmacol ; 11: 615972, 2020.
Article in English | MEDLINE | ID: covidwho-1004690

ABSTRACT

Background: Interleukin-6 (IL-6) is known to be detrimental in coronavirus disease 2019 (COVID-19) because of its involvement in driving cytokine storm. This systematic review and meta-analysis aimed to assess the safety and efficacy of anti-IL-6 signaling (anti-IL6/IL-6R/JAK) agents on COVID-19 based on the current evidence. Methods: Studies were identified through systematic searches of PubMed, EMBASE, ISI Web of Science, Cochrane library, ongoing clinical trial registries (clinicaltrials.gov), and preprint servers (medRxiv, ChinaXiv) on August 10, 2020, as well as eligibility checks according to predefined selection criteria. Statistical analysis was performed using Review Manager (version 5.3) and STATA 12.0. Results: Thirty-one studies were included in the pooled analysis of mortality, and 12 studies were identified for the analysis of risk of secondary infections. For mortality analysis, 5630 COVID-19 cases including 2,132 treated patients and 3,498 controls were analyzed. Anti-IL-6 signaling agents plus standard of care (SOC) significantly decreased the mortality rate compared to SOC alone (pooled OR = 0.61, 95% CI 0.45-0.84, p = 0.002). For the analysis of secondary infection risk, 1,624 patients with COVID-19 including 639 treated patients and 985 controls were included, showing that anti-IL-6 signaling agents did not increase the rate of secondary infections (pooled OR = 1.21, 95% CI 0.70-2.08, p = 0.50). By contrast, for patients with critical COVID-19 disease, anti-IL-6 signaling agents failed to reduce mortality compared to SOC alone (pooled OR = 0.75, 95% CI 0.42-1.33, p = 0.33), but they tended to increase the risk of secondary infections (pooled OR = 1.85, 95% CI 0.95-3.61, p = 0.07). A blockade of IL-6 signaling failed to reduce the mechanical ventilation rate, ICU admission rate, or elevate the clinical improvement rate. Conclusion: IL-6 signaling inhibitors reduced the mortality rate without increasing secondary infections in patients with COVID-19 based on current studies. For patients with critical disease, IL-6 signaling inhibitors did not exhibit any benefit.

19.
Preprint in English | bioRxiv | ID: ppbiorxiv-424961

ABSTRACT

Host-virus protein-protein interaction is the key component of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle. We conducted a comprehensive interactome study between the virus and host cells using tandem affinity purification and proximity labeling strategies and identified 437 human proteins as the high-confidence interacting proteins. Functional characterization and further validation of these interactions elucidated how distinct SARS-CoV-2 viral proteins participate in its lifecycle, and discovered potential drug targets to the treatment of COVID-19. The interactomes of two key SARS-CoV-2 encoded viral proteins, NSP1 and N protein, were compared with the interactomes of their counterparts in other human coronaviruses. These comparisons not only revealed common host pathways these viruses manipulate for their survival, but also showed divergent protein-protein interactions that may explain differences in disease pathology. This comprehensive interactome of coronavirus disease-2019 provides valuable resources for understanding and treating this disease.

20.
Cell Prolif ; 54(1): e12953, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-991253

ABSTRACT

OBJECTIVES: Using strategy of drug repurposing, antiviral agents against influenza A virus (IAV) and newly emerging SARS-coronavirus 2 (SARS-CoV-2, also as 2019-nCoV) could be quickly screened out. MATERIALS AND METHODS: A previously reported engineered replication-competent PR8 strain carrying luciferase reporter gene (IAV-luc) and multiple pseudotyped IAV and SARS-CoV-2 virus was used. To specifically evaluate the pH change of vesicles containing IAV, we constructed an A549 cell line with endosomal and lysosomal expression of pHluorin2. RESULTS: Here, we identified azithromycin (AZ) as an effective inhibitor against multiple IAV and SARS-CoV-2 strains. We found that AZ treatment could potently inhibit IAV infection in vitro. Moreover, using pseudotyped virus model, AZ could also markedly block the entry of SARS-CoV-2 in HEK293T-ACE2 and Caco2 cells. Mechanistic studies further revealed that such effect was independent of interferon signalling. AZ treatment neither impaired the binding and internalization of IAV virions, nor the viral replication, but rather inhibited the fusion between viral and vacuolar membranes. Using a NPC1-pHluorin2 reporter cell line, we confirmed that AZ treatment could alkalize the vesicles containing IAV virions, thereby preventing pH-dependent membrane fusion. CONCLUSIONS: Overall, our findings demonstrate that AZ can exert broad-spectrum antiviral effects against IAV and SARS-CoV-2, and could be served as a potential clinical anti-SARS-CoV-2 drug in emergency as well as a promising lead compound for the development of next-generation anti-IAV drugs.


Subject(s)
Antiviral Agents/pharmacology , Azithromycin/pharmacology , COVID-19/metabolism , Influenza A virus/metabolism , Influenza, Human/metabolism , SARS-CoV-2/metabolism , Virus Internalization/drug effects , A549 Cells , COVID-19/drug therapy , COVID-19/genetics , Caco-2 Cells , HEK293 Cells , HeLa Cells , Humans , Influenza A virus/genetics , Influenza, Human/drug therapy , Influenza, Human/genetics , Interferons/genetics , Interferons/metabolism , SARS-CoV-2/genetics , Signal Transduction/drug effects , Signal Transduction/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...