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1.
Eur J Pharm Sci ; : 105631, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33115675

RESUMO

BACKGROUND: Effective antiviral drugs for COVID-19 are still lacking. This study aims to evaluate the clinical outcomes and plasma concentrations of baloxavir acid and favipiravir in COVID-19 patients. METHODS: Favipiravir and baloxavir acid were evaluated for their antiviral activity against SARS-CoV-2 in vitro before the trial initiation. We conducted an exploratory trial with 3 arms involving hospitalized adult patients with COVID-19. Patients were randomized assigned in a 1:1:1 ratio into baloxavir marboxil group, favipiravir group, and control group. The primary outcome was the percentage of subjects with viral negative by Day 14 and the time from randomization to clinical improvement. Virus load reduction, blood drug concentration and clinical presentation were also observed. The trial was registered with Chinese Clinical Trial Registry (ChiCTR 2000029544). RESULTS: Baloxavir acid showed antiviral activity in vitro with the half-maximal effective concentration (EC50) of 5.48 µM comparable to arbidol and lopinavir, but favipiravir didn't demonstrate significant antiviral activity up to 100 µM. Thirty patients were enrolled. The percentage of patients who turned viral negative after 14-day treatment was 70%, 77%, and 100% in the baloxavir marboxil, favipiravir, and control group respectively, with the medians of time from randomization to clinical improvement was 14, 14 and 15 days, respectively. One reason for the lack of virological effect and clinical benefits may be due to insufficient concentrations of these drugs relative to their antiviral activities. One of the limitations of this study is the time from symptom onset to randomization, especially in the baloxavir marboxil and control groups, which is higher than the favipiravir group. CONCLUSIONS: Our findings could not prove a benefit of addition of either baloxavir marboxil or favipiravir under the trial dosages to the existing standard treatment.

2.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(4): 531-536, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32985168

RESUMO

Clinical trial management system is independently developed by our hospital, which basically realized the whole process management and data collection of clinical trials. Based on the platform, the functional architecture of data remote monitoring and auditing was established. By desensitizing and encrypting of data, the project and subject hologram were visualized to facilitate to review of data. The data remote monitoring and auditing cloud platform adopts the B/S architecture pattern. Users register to apply for an account through the cloud platform, and access to the account via HTTPS security protocol. The authorized users were able to view the relevant items online to ensure the secure data transmission and easy operating. The electronic management of data is the direction of future efforts. By compliance with laws and regulations, the remote monitoring/auditing can be realized, and the data security and personal privacy can be ensured with the application of information technology. In this paper, the feasibility of remote monitoring/auditing mode is explored, specific technical schemes and system functions are suggested, and the realization scenarios are conceived in case of major public health emergencies.


Assuntos
Ensaios Clínicos como Assunto , Auditoria Administrativa , Consulta Remota , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Segurança Computacional
3.
Infect Dis Ther ; 9(4): 927-934, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32964392

RESUMO

INTRODUCTION: Enterococcus faecalis is a significant cause of nosocomial infections and is difficult to treat because of intrinsic and acquired resistance to many antibiotics. In addition, the emergence of linezolid-resistant E. faecalis (LZR-Efa) is reducing the choices available for anti-infective therapy. The aim of this study was to examine the in vitro antibacterial effects of fosfomycin (FM), vancomycin (VAN) and daptomycin (DAP), alone and in combination, against LZR-Efa. METHODS: Five LZR-Efa strains and E. faecalis ATCC 29212 were studied. The antibacterial effects of FM, and of FM, VAN and DAP, were assessed using the time-kill assay. Biofilm formation and elimination were evaluated by crystal violet staining. RESULTS: When used at concentrations greater than 0.5 × MIC, FM did not produce dose-dependent effects against LZR-Efa isolates. The use of DAP (47.1 mg/L) alone, and FM (83 mg/L) combined with DAP (20.6 mg/L), produced a persistent inhibitory effect against both planktonic LZR-Efa isolates and those forming biofilms. In addition, FM and VAN combined with glucose-6-phosphate produced visible eradication effects against biofilms grown for 24 h, while DAP alone or combined with FM resulted in the best eradication activity against biofilms grown for 72 h prior to exposure. CONCLUSION: The use of FM combined with DAP provided the best potential therapeutic option for treating LZR-Efa infections out of those tested. In addition, the optimum treatment for biofilm elimination depended on the stage of biofilm formation.

4.
Comput Struct Biotechnol J ; 18: 2012-2025, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802273

RESUMO

Cancer proteomics has become a powerful technique for characterizing the protein markers driving transformation of malignancy, tracing proteome variation triggered by therapeutics, and discovering the novel targets and drugs for the treatment of oncologic diseases. To facilitate cancer diagnosis/prognosis and accelerate drug target discovery, a variety of methods for tumor marker identification and sample classification have been developed and successfully applied to cancer proteomic studies. This review article describes the most recent advances in those various approaches together with their current applications in cancer-related studies. Firstly, a number of popular feature selection methods are overviewed with objective evaluation on their advantages and disadvantages. Secondly, these methods are grouped into three major classes based on their underlying algorithms. Finally, a variety of sample separation algorithms are discussed. This review provides a comprehensive overview of the advances on tumor maker identification and patients/samples/tissues separations, which could be guidance to the researches in cancer proteomics.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32837749

RESUMO

The real-time reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA from sputum or nasopharyngeal swab had a relatively low positive rate in the early stage of coronavirus disease 2019 (COVID-19). Meanwhile, the manifestations of COVID-19 as seen through computed tomography (CT) imaging show individual characteristics that differ from those of other types of viral pneumonia such as Influenza-A viral pneumonia (IAVP). This study aimed to establish an early screening model to distinguish COVID-19 pneumonia from IAVP and healthy cases through pulmonary CT images using deep learning techniques. A total of 618 CT samples were collected: 219 samples from 110 patients with COVID-19 (mean age 50 years; 63 (57.3%) male patients); 224 samples from 224 patients with IAVP (mean age 61 years; 156 (69.6%) male patients); and 175 samples from 175 healthy cases (mean age 39 years; 97 (55.4%) male patients). All CT samples were contributed from three COVID-19-designated hospitals in Zhejiang Province, China. First, the candidate infection regions were segmented out from the pulmonary CT image set using a 3D deep learning model. These separated images were then categorized into the COVID-19, IAVP, and irrelevant to infection (ITI) groups, together with the corresponding confidence scores, using a location-attention classification model. Finally, the infection type and overall confidence score for each CT case were calculated using the Noisy-or Bayesian function. The experimental result of the benchmark dataset showed that the overall accuracy rate was 86.7% in terms of all the CT cases taken together. The deep learning models established in this study were effective for the early screening of COVID-19 patients and were demonstrated to be a promising supplementary diagnostic method for frontline clinical doctors.

6.
Biomed Pharmacother ; 130: 110556, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763815

RESUMO

BACKGROUNDS: Ribonucleotide reductase (RR) catalyzes the essential step in the formation of all four deoxynucleotides. Upregulated activity of RR plays an active role in tumor progression. As the regulatory subunit of RR, ribonucleotide reductase subunit M2 (RRM2) is regarded as one of the effective therapeutic targets for DNA replication-dependent diseases, such as cancers. Recent studies have revealed that osalmid significantly inhibits the activity of RRM2, but the metabolic profile of osalmid remains unknown. OBJECTIVE: The aim of this study was to clarify the metabolic profile including metabolites, isoenzymes and metabolic pathways of osalmid. The anti-human hepatocellular carcinoma activity and mechanism of metabolites were further investigated. MATERIALS AND METHODS: Ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) was used for identifying metabolites and for characterizing phase I and phase II metabolic pathways with recombinant enzymes or in human liver microsomes of osalmid. The eHiTS docking system was used for potential RRM2 inhibitor screening among metabolites. Cytotoxicity assays were performed for evaluating cell proliferation inhibitory activity of metabolites. Cell cycle assays and cell apoptosis assays were assessed by flow cytometry. Western blotting analysis of RRM2, cyclin D1, p21, p53, phosphorylated p53, Bcl-2 and Bax was performed to explore the anti-hepatocellular carcinoma mechanism of the active metabolites. RESULTS: Ten metabolites of osalmid were identified, and none of them have been reported previously. Hydroxylation, glucuronidation, sulfonation, acetylation and degradation were recognized as the main metabolic processes of osalmid. Isozymes of CYP1A2, CYP2C9, UGT1A1, UGT1A6, UGT1A9, UGT2B7 and UGT2B15 were involved in phase I and phase II metabolism of osalmid. Metabolites M7, M8 and M10 showed higher binding affinities with the RRM2 active site than osalmid. Metabolite M7 exhibited potent inhibitory activity to hepatocellular carcinoma cell lines by both competitive inhibition and down-regulation of RRM2. Moreover, M7 significantly induced cell cycle arrest and apoptosis by activating p53-related pathways. CONCLUSIONS: The metabolic profile of osalmid was identified. M7 significantly inhibited human hepatocellular carcinoma progression by inhibiting RRM2 activity. Furthermore, M7 induced cell cycle arrest and apoptosis by activating p53-related signaling pathways.

7.
Am J Gastroenterol ; 115(7): 1075-1083, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32618658

RESUMO

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.


Assuntos
Infecções por Coronavirus , Hepatite Viral Humana/enzimologia , Testes de Função Hepática , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Estudos Transversais , Feminino , Hepatite Viral Humana/virologia , Humanos , Hepatopatias/enzimologia , Hepatopatias/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Estudos Retrospectivos , Fatores de Risco
8.
Am J Gastroenterol ; 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: covidwho-459522

RESUMO

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

9.
J Infect Dis ; 2020 May 31.
Artigo em Inglês | MEDLINE | ID: covidwho-436918

RESUMO

The viral RNA shedding time of SARS-CoV-2 has not been well characterized. Clinical data were collected and compared between patients with short and long viral RNA shedding (in the first and last quarter). The probability of recurrent positive RT-PCR results decreased sharply to 4.8% after three consecutive negatives. At least three consecutive negatives were suitable for the criteria of end of viral RNA shedding. The viral RNA shedding from respiratory tract in patients with normal B cell count was significantly shorter than patients with decreased B cell on admission (median [IQR], 11[9-13] vs 16[12-20] days, P=0.001).

10.
Medicine (Baltimore) ; 99(26): e21012, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: covidwho-616558

RESUMO

COVID-19 is an emerging infectious disease capable of causing severe pneumonia. We aimed to characterize a group of critically ill patients in a single-center study.This was a retrospective case series of 23 patients with confirmed COVID-19-related critical illness in the intensive care unit (ICU) of a hospital in Hangzhou Zhejiang Province between January 22 and March 20, 2020.Of the 23 critically ill patients, the median age was 66 years (interquartile range [IQR] 59-80 years). The median time from disease onset to ICU admission was 10 days (IQR 6-11 days), to mechanical ventilation (MV) was 11 days (IQR 7.75-13 days), to artificial liver plasma exchange was 12 days (IQR 9.75-14.75 days), and to extracorporeal membrane oxygenation (ECMO) was 22 days (IQR 17.5-30 days). Nine patients required high flow oxygen. Fourteen patients received MV. Six required ECMO. Nine received artificial liver plasma exchange. Mortality was 0 at day 28.Mortality was 0 at day 28 in our single-center study. Extracorporeal membrane oxygenation reduced the requirements for ventilator support. Artificial liver plasma exchange significantly reduced inflammatory cytokine levels. These supportive therapies helped to extend the patients' survival times and increase the chance of follow-up treatments.

11.
Emerg Microbes Infect ; : 1-74, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: covidwho-599992

RESUMO

The mutations in the SARS-CoV-2 virus genome during the spread of COVID-19 have been unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases, increased liver/kidney damage, and prolonged period of nuclear acid positivity, compared with patients in Wuhan, China. To investigate the underlying mechanisms, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified by gene alignment. Further phylogenetic analysis and relative synonymous codon usage heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 virus strains collected globally based on the base (C or T) at positions 8824 and 28247. ZJ01 has T at both sites and is currently the only known TT type. The prediction of the Furin cleavage site (FCS) and sequence alignment of the virus family indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was higher in the whole body, especially in glands, liver, kidneys, and colon. Thus, FCS may help SARS-CoV-2 infect these organs. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 (the source of FCS sequence-PRRA) caused mild flu-like symptoms, further showing potential in differentiating into mild COVID-19 subtypes.

12.
J Med Internet Res ; 22(6): e19786, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: covidwho-599698

RESUMO

BACKGROUND: The coronavirus disease (COVID-19) has become an urgent and serious global public health crisis. Community engagement is the first line of defense in the fight against infectious diseases, and general practitioners (GPs) play an important role in it. GPs are facing unique challenges from disasters and pandemics in delivering health care. However, there is still no suitable mobile management system that can help GPs collect data, dynamically assess risks, and effectively triage or follow-up with patients with COVID-19. OBJECTIVE: The aim of this study is to design, develop, and deploy a mobile-based decision support system for COVID-19 (DDC19) to assist GPs in collecting data, assessing risk, triaging, managing, and following up with patients during the COVID-19 outbreak. METHODS: Based on the actual scenarios and the process of patients using health care, we analyzed the key issues that need to be solved and designed the main business flowchart of DDC19. We then constructed a COVID-19 dynamic risk stratification model with high recall and clinical interpretability, which was based on a multiclass logistic regression algorithm. Finally, through a 10-fold cross-validation to quantitatively evaluate the risk stratification ability of the model, a total of 2243 clinical data consisting of 36 dimension clinical features from fever clinics were used for training and evaluation of the model. RESULTS: DDC19 is composed of three parts: mobile terminal apps for the patient-end and GP-end, and the database system. All mobile terminal devices were wirelessly connected to the back end data center to implement request sending and data transmission. We used low risk, moderate risk, and high risk as labels, and adopted a 10-fold cross-validation method to evaluate and test the COVID-19 dynamic risk stratification model in different scenarios (different dimensions of personal clinical data accessible at an earlier stage). The data set dimensions were (2243, 15) when only using the data of patients' demographic information, clinical symptoms, and contact history; (2243, 35) when the results of blood tests were added; and (2243, 36) after obtaining the computed tomography imaging results of the patient. The average value of the three classification results of the macro-area under the curve were all above 0.71 in each scenario. CONCLUSIONS: DCC19 is a mobile decision support system designed and developed to assist GPs in providing dynamic risk assessments for patients with suspected COVID-19 during the outbreak, and the model had a good ability to predict risk levels in any scenario it covered.

13.
J Med Internet Res ; 22(6): e19786, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32540845

RESUMO

BACKGROUND: The coronavirus disease (COVID-19) has become an urgent and serious global public health crisis. Community engagement is the first line of defense in the fight against infectious diseases, and general practitioners (GPs) play an important role in it. GPs are facing unique challenges from disasters and pandemics in delivering health care. However, there is still no suitable mobile management system that can help GPs collect data, dynamically assess risks, and effectively triage or follow-up with patients with COVID-19. OBJECTIVE: The aim of this study is to design, develop, and deploy a mobile-based decision support system for COVID-19 (DDC19) to assist GPs in collecting data, assessing risk, triaging, managing, and following up with patients during the COVID-19 outbreak. METHODS: Based on the actual scenarios and the process of patients using health care, we analyzed the key issues that need to be solved and designed the main business flowchart of DDC19. We then constructed a COVID-19 dynamic risk stratification model with high recall and clinical interpretability, which was based on a multiclass logistic regression algorithm. Finally, through a 10-fold cross-validation to quantitatively evaluate the risk stratification ability of the model, a total of 2243 clinical data consisting of 36 dimension clinical features from fever clinics were used for training and evaluation of the model. RESULTS: DDC19 is composed of three parts: mobile terminal apps for the patient-end and GP-end, and the database system. All mobile terminal devices were wirelessly connected to the back end data center to implement request sending and data transmission. We used low risk, moderate risk, and high risk as labels, and adopted a 10-fold cross-validation method to evaluate and test the COVID-19 dynamic risk stratification model in different scenarios (different dimensions of personal clinical data accessible at an earlier stage). The data set dimensions were (2243, 15) when only using the data of patients' demographic information, clinical symptoms, and contact history; (2243, 35) when the results of blood tests were added; and (2243, 36) after obtaining the computed tomography imaging results of the patient. The average value of the three classification results of the macro-area under the curve were all above 0.71 in each scenario. CONCLUSIONS: DCC19 is a mobile decision support system designed and developed to assist GPs in providing dynamic risk assessments for patients with suspected COVID-19 during the outbreak, and the model had a good ability to predict risk levels in any scenario it covered.


Assuntos
Infecções por Coronavirus/diagnóstico , Sistemas de Apoio a Decisões Clínicas , Medicina Geral/métodos , Clínicos Gerais , Aplicativos Móveis , Pneumonia Viral/diagnóstico , Medição de Risco/métodos , Triagem/métodos , Betacoronavirus , Assistência à Saúde/métodos , Surtos de Doenças , Feminino , Humanos , Masculino , Pandemias , Prognóstico , Saúde Pública/métodos
14.
Medicine (Baltimore) ; 99(26): e21012, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590819

RESUMO

COVID-19 is an emerging infectious disease capable of causing severe pneumonia. We aimed to characterize a group of critically ill patients in a single-center study.This was a retrospective case series of 23 patients with confirmed COVID-19-related critical illness in the intensive care unit (ICU) of a hospital in Hangzhou Zhejiang Province between January 22 and March 20, 2020.Of the 23 critically ill patients, the median age was 66 years (interquartile range [IQR] 59-80 years). The median time from disease onset to ICU admission was 10 days (IQR 6-11 days), to mechanical ventilation (MV) was 11 days (IQR 7.75-13 days), to artificial liver plasma exchange was 12 days (IQR 9.75-14.75 days), and to extracorporeal membrane oxygenation (ECMO) was 22 days (IQR 17.5-30 days). Nine patients required high flow oxygen. Fourteen patients received MV. Six required ECMO. Nine received artificial liver plasma exchange. Mortality was 0 at day 28.Mortality was 0 at day 28 in our single-center study. Extracorporeal membrane oxygenation reduced the requirements for ventilator support. Artificial liver plasma exchange significantly reduced inflammatory cytokine levels. These supportive therapies helped to extend the patients' survival times and increase the chance of follow-up treatments.


Assuntos
Infecções por Coronavirus/terapia , Oxigenação por Membrana Extracorpórea , Fígado Artificial , Pneumonia Viral/terapia , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/complicações , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Estudos Retrospectivos
15.
Emerg Microbes Infect ; 9(1): 1474-1488, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32543348

RESUMO

The mutations in the SARS-CoV-2 virus genome during COVID-19 dissemination are unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases compared with patients in Wuhan. For mechanisms exploration, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified. Phylogenetic and relative synonymous codon usage analysis suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 global virus strains based on the base (C or T) at positions 8824 and 28247 while ZJ01 has T at both sites. The prediction of the Furin cleavage site (FCS) and sequence alignment indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was especially higher in glands, liver, kidneys, and colon. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 caused mild flu-like symptoms, further showing its potential in differentiating into mild COVID-19 subtypes.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Furina/metabolismo , Pneumonia Viral/virologia , Adulto , Betacoronavirus/genética , China/epidemiologia , Códon , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Progressão da Doença , Evolução Molecular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Pandemias , Filogenia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Análise de Sequência de RNA
16.
J Infect Dis ; 222(3): 367-371, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32474608

RESUMO

The viral RNA shedding time (VST) for severe acute respiratory syndrome coronavirus 2 has not been well characterized. Clinical data were collected and compared between patients with short and long VSTs (in the lower and upper quartiles, respectively). The probability of recurrent positive reverse-transcription polymerase chain reaction results decreased sharply to 4.8% after 3 consecutive negative results. A series of ≥3 consecutive negative results was suitable as a criterion for the end of viral RNA shedding. The VST for shedding from the respiratory tract was significantly shorter in patients with normal B-cell counts on admission than in those with decreased B-cell counts (median [interquartile range], 11 [9-13] vs 16 [12-20] days, respectively; P = .001).


Assuntos
Linfócitos B/fisiologia , Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Sistema Respiratório/virologia , Eliminação de Partículas Virais , Betacoronavirus/imunologia , Estudos de Casos e Controles , China , Citocinas/metabolismo , Feminino , Humanos , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Modelos de Riscos Proporcionais , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
17.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 158-169, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: covidwho-239782

RESUMO

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6), and Management of COVID-19: the Zhejiang experience, we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.


Assuntos
Infecções por Coronavirus , Tratamento Farmacológico , Pandemias , Pneumonia Viral , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Estado Terminal , Humanos , Apoio Nutricional , Pneumonia Viral/tratamento farmacológico , Probióticos/administração & dosagem
18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 147-157, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: covidwho-233476

RESUMO

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as Lactobacillus and Bifidobacterium, so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.


Assuntos
Infecções por Coronavirus , Gerenciamento Clínico , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Diagnóstico Precoce , Fezes/virologia , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Escarro/virologia
19.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 147-157, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32391658

RESUMO

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as Lactobacillus and Bifidobacterium, so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.


Assuntos
Infecções por Coronavirus , Gerenciamento Clínico , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Diagnóstico Precoce , Fezes/virologia , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Escarro/virologia
20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 158-169, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32391659

RESUMO

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6), and Management of COVID-19: the Zhejiang experience, we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.


Assuntos
Infecções por Coronavirus , Tratamento Farmacológico , Pandemias , Pneumonia Viral , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Estado Terminal , Humanos , Apoio Nutricional , Pneumonia Viral/tratamento farmacológico , Probióticos/administração & dosagem
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