PLoS Neglected Tropical Diseases
·
2020
·Vol. 14
·期 8
·e0008648
·
IF 3.885
Jiazhen Zheng,Rui Zhou,Fengjuan Chen,Guofang Tang,Keyi Wu,Furong Li,Huamin Liu,Jianyun Lu,Jiyuan Zhou,Ziying Yang,Yuxin Yuan,Chunliang Lei,Xianbo Wu
The phenomenon of COVID-19 patients tested positive for SARS-CoV-2 after discharge (redetectable as positive, RP) emerged globally. The data of incidence rate and risk factors for RP event and the clinical features of RP patients may provide recommendations for virus containment and cases management for COVID-19. We prospectively collected and analyzed the epidemiological, clinical and virological data from 285 adult patients with COVID-19 and acquired their definite clinical outcome (getting PCR positive or not during post-discharge surveillance). By March 10, 27 (9.5%) discharged patients had tested positive for SARS-CoV-2 in their nasopharyngeal swab after a median duration of 7·0 days (IQR 5·0–8·0). Compared to first admission, RP patients generally had milder clinical symptoms, lower viral load, shorter length of stay and improved pulmonary conditions at readmission (p<0.05). Elder RP patients (≥ 60 years old) were more likely to be symptomatic compared to younger patients (7/8, 87.5% vs . 3/19, 18.8%, p = 0.001) at readmission. Age, sex, epidemiological history, clinical symptoms and underlying diseases were similar between RP and non-RP patients (p>0.05). A prolonged duration of viral shedding (>10 days) during the first hospitalization [adjusted odds ratio [aOR]: 5.82, 95% confidence interval [CI]: 2.50–13.57 for N gene; aOR: 9.64, 95% CI: 3.91–23.73 for ORF gene] and higher Ct value (ORF) in the third week of the first hospitalization (aOR: 0.69; 95% CI: 0.50–0.95) were associated with RP events. In conclusion, RP events occurred in nearly 10% of COVID-19 patients shortly after the negative tests, were not associated with worsening symptoms and unlikely reflect reinfection. Patients’ lack of efficiency in virus clearance was a risk factor for RP result. It is noteworthy that elder RP patients (≥ 60 years old) were more susceptible to clinical symptoms at readmission.
The baseline enrolled 285 patients admitted to Guangzhou Eighth People’s Hospital (Guangzhou, Guangdong) with a diagnosis of COVID-19. We reported the epidemiology, clinical laboratory, radiological characteristics, virological results, treatment, and definite outcomes (getting PCR retested positive (RP) or not during post-discharge surveillance) of the cases. RP events occurred in nearly 10% of cases, were not associated with worsening symptoms and unlikely reflect reinfection. The lack of efficiency in virus clearance was a risk factor for RP result. Elder RP patients (≥ 60 years old) were more susceptible to clinical symptom at readmission. In the context of numerous COVID-19 cases showed SARS-CoV-2 positive again after discharged, the data in China may provide recommendations for post-discharge management, especially for other developing countries.
研究领域:
流行病学
·
传染病学
·
公共卫生
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DOI
PubMed
高影响因子
IEEE Access
·
2020
·
IF 3.745
Shaoping Hu,Yuan Gao,Zhangming Niu,Yinghui Jiang,Lao Li,Xianglu Xiao,Minhao Wang,Evandro Fei Fang,Wade Menpes-Smith,Jun Xia,Hui Ye,Guang Yang
An outbreak of a novel coronavirus disease (i.e., COVID-19) has been recorded in Wuhan, China since late December 2019, which subsequently became pandemic around the world. Although COVID-19 is an acutely treated disease, it can also be fatal with a risk of fatality of 4.03% in China and the highest of 13.04% in Algeria and 12.67% Italy (as of 8th April 2020). The onset of serious illness may result in death as a consequence of substantial alveolar damage and progressive respiratory failure. Although laboratory testing, e.g., using reverse transcription polymerase chain reaction (RT-PCR), is the golden standard for clinical diagnosis, the tests may produce false negatives. Moreover, under the pandemic situation, shortage of RT-PCR testing resources may also delay the following clinical decision and treatment. Under such circumstances, chest CT imaging has become a valuable tool for both diagnosis and prognosis of COVID-19 patients. In this study, we propose a weakly supervised deep learning strategy for detecting and classifying COVID-19 infection from CT images. The proposed method can minimise the requirements of manual labelling of CT images but still be able to obtain accurate infection detection and distinguish COVID-19 from non-COVID-19 cases. Based on the promising results obtained qualitatively and quantitatively, we can envisage a wide deployment of our developed technique in large-scale clinical studies.
研究领域:
放射学
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传染病学
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医学影像处理
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人工智能在医学中的应用
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呼吸系统疾病
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DOI
高影响因子
BMC PUBLIC HEALTH
·
2021
·Vol. 21
·期 1
·2001
·
IF 3.295
Mao Zijun,Zou Qi,Yao Hong,Wu Jingyi
Background As COVID-19 continues to spread globally, traditional emergency management measures are facing many practical limitations. The application of big data analysis technology provides an opportunity for local governments to conduct the COVID-19 epidemic emergency management more scientifically. The present study, based on emergency management lifecycle theory, includes a comprehensive analysis of the application framework of China’s SARS epidemic emergency management lacked the support of big data technology in 2003. In contrast, this study first proposes a more agile and efficient application framework, supported by big data technology, for the COVID-19 epidemic emergency management and then analyses the differences between the two frameworks. Methods This study takes Hainan Province, China as its case study by using a file content analysis and semistructured interviews to systematically comprehend the strategy and mechanism of Hainan’s application of big data technology in its COVID-19 epidemic emergency management. Results Hainan Province adopted big data technology during the four stages, i.e., migration, preparedness, response, and recovery, of its COVID-19 epidemic emergency management. Hainan Province developed advanced big data management mechanisms and technologies for practical epidemic emergency management, thereby verifying the feasibility and value of the big data technology application framework we propose. Conclusions This study provides empirical evidence for certain aspects of the theory, mechanism, and technology for local governments in different countries and regions to apply, in a precise, agile, and evidence-based manner, big data technology in their formulations of comprehensive COVID-19 epidemic emergency management strategies.
研究领域:
公共卫生
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应急管理体系
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信息科学
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流行病学
·
数据驱动决策
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DOI
高影响因子
VIROLOGY
·
2022
·
IF 3.513
Haohao Yan,Zhicheng Liu,Gangan Yan,Xiaoli Liu,Xiaoping Liu,Yanchang Wang,Yunyu Chen
The global scourge of COVID-19 is a serious threat to public health, but effective therapies remain very limited for this disease. Therefore, the discovery of novel antiviral agents is urgently needed to fight against COVID-19. In the lifecycle of SARS-CoV-2, the causing pathogen of COVID-19, papain-like protease (PLpro) is responsible for the cleavage of polyprotein into functional units as well as immune evasion of vaccines. Hence, PLpro has been regarded as an attractive target to develop antiviral agents. Herein, we first developed a robust and simple sandwich-like fluorescence polarization (FP) screening assay for the discovery of PLpro inhibitors, and identified anacardic acid as a novel competitive inhibitor against PLpro in vitro with an IC 50 value of 24.26 ± 0.4 μM. This reliable FP screening assay could provide a prospective avenue for rapid discovery of antiviral agents targeting PLpro in a large-scale screening.
研究领域:
病毒学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
THERAPEUTIC DRUG MONITORING
·
2025
·
IF 2.4
Ma Zhiyuan,Bai Mengru,Shen Shuying,Zhou Junshan,Dong Rong,Zhang Jiangjun,Weng Yayun,Li Li,Li Yongchen,Liu Dan,Yan Wei,Lin Nengming,Xia Jianmei
Background: Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk of progression to severe disease. However, data on the real-world plasma exposure to nirmatrelvir/ritonavir remain limited, particularly in Chinese patients. This study aimed to assess the nirmatrelvir/ritonavir trough concentration (C trough ) and identify its critical factors in hospitalized Chinese patients treated with nirmatrelvir/ritonavir 300 mg/100 mg twice daily over a 5-day course. Methods: A high-performance liquid chromatography-tandem mass spectrometry assay was developed and validated to measure the nirmatrelvir/ritonavir C trough . Correlation analyses were performed to identify the variables influencing nirmatrelvir/ritonavir C trough . Results: Among the 110 patients, 100% had plasma concentrations above the antiviral in vitro 90% effective concentration. The median C trough of nirmatrelvir was 4.55 mcg/mL (15.6× 90% effective concentration), ranging from 0.65 to 12.44 mcg/mL. Nirmatrelvir C trough in normal and mild renal impairment cohorts were comparable (4.09 ± 1.97 mcg/mL and 4.57 ± 2.21 mcg/mL) but significantly increased in the moderate renal impairment cohort (6.41 ± 2.31 mcg/mL). Sex, age, and obesity were not significantly associated with nirmatrelvir exposure. Conclusions: Nirmatrelvir C trough was high in Chinese patients with COVID-19, and therapeutic drug monitoring should not be routinely recommended, except in patients with renal impairment.
研究领域:
药理学
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传染病
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临床研究
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产品关联
DOI
PubMed
高影响因子
Smart Medicine
·
2023
·Vol. 2
·期 1
·e20220035
·
IF 0
Changmin Shao,Ting Cao,Xiaochen Wang,Qihui Fan,Fangfu Ye
The lung is the respiratory organ of the human body, and the alveoli are the most basic functional units of the lung. Herein, a photo-responsive stretchable Janus membrane was proposed for the reconstruction of the alveolar–capillary barrier in vitro. This Janus membrane was fabricated by photocrosslinking methylacrylamide gelatin (Gelma) hydrogel and N-isoacrylamide (NIPAM) hydrogel mixed with graphene oxide (GO). The Gelma hydrogel containing large amounts of collagen provides a natural extracellular matrix environment for cell growth, while the temperature-sensitive NIPAM hydrogel combined with GO gives the membrane a light-controlled stretching property. Based on this Janus membrane, an open polydimethylsiloxane chip was established to coculture alveolar epithelial cells and vascular endothelial cells at the air–liquid interface. It was demonstrated that the alveolar epithelial cells cultured on the upper side of the Janus membrane could express epithelial cell marker protein E-cadherin and secrete alveolar surfactant. In addition, VE-cadherin, an endothelium-specific protein located at the junction between endothelial cells, was also detected in vascular endothelial cells cultured on the underside of Janus membrane. The constructed lung tissue model with the dynamically stretchable Janus membrane is well-suited for COVID-19 infection studies and drug testing.
研究领域:
生物医学工程
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组织工程
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呼吸系统疾病
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细胞培养
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DOI
Cell Metabolism
·
2024
·
IF 27.7
Kan Huang,Zilun Li,Xi He,Jun Dai,Bingding Huang,Yongxia Shi,Dongxiao Fan,Zefeng Zhang,Yunchong Liu,Na Li,Zhongyu Zhang,Jiangyun Peng,Chenshu Liu,Renli Zeng,Zhipeng Cen,Tengyao Wang,Wenchao Yang,Meifeng Cen,Jingyu Li,Shuai Yuan,Lu Zhang,Dandan Hu,Shuxiang Huang,Pin Chen,Peilong Lai,Liyan Lin,Jielu Wen,Zhengde Zhao,Xiuyi Huang,Lining Yuan,Lifang Zhou,Haoliang Wu,Lihua Huang,Kai Feng,Jian Wang,Baolin Liao,Weiping Cai,Xilong Deng,Yueping Li,Jianping Li,Zhongwei Hu,Li Yang,Jiaojiao Li,Youguang Zhuo,Fuchun Zhang,Lin Lin,Yifeng Luo,Wei Zhang,Qianlin Ni,Xiqiang Hong,Guangqi Chang,Yang Zhang,Dongxian Guan,Weikang Cai,Yutong Lu,Fang Li,Li Yan,Meng Ren,Linghua Li,Sifan Chen
Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2β1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2β1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.
研究领域:
心血管研究
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微生物组学研究
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血栓机制
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代谢组学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2021
·Vol. 43
·期 7
·1749-1757
·
IF 6.15
Li Dan,Ding Jin,Liu Te-li,Wang Feng,Meng Xiang-xi,Liu Song,Yang Zhi,Zhu Hua
The spike protein of SARS-CoV-2 interacts with angiotensin-converting enzyme 2 (ACE2) of human respiratory epithelial cells, which leads to infection. Furthermore, low-dose radiation has been found to reduce inflammation and aid the curing of COVID-19. The receptor binding domain (RBD), a recombinant spike protein with a His tag at the C-terminus, binds to ACE2 in human body. We thus constructed a radioiodinated RBD as a molecule-targeted probe to non-invasively explore ACE2 expression in vivo, and to investigate radiotherapy pathway for inhibiting ACE2. RBD was labeled with [ 124 I]NaI using an N-bromosuccinimide (NBS)-mediated method, and 124 I-RBD was obtained after purification with a specific activity of 28.9 GBq/nmol. Its radiochemical purity was (RCP) over 90% in saline for 5 days. The dissociation constant of 124 I-RBD binding to hACE2 was 75.7 nM. The uptake of 124 I-RBD by HeLa ACE+ cells at 2 h was 2.96% ± 0.35%, which could be substantially blocked by an excessive amount of RBD, and drop to 1.71% ± 0.23%. In BALB/c mice, the biodistribution of 124 I-RBD after intravenous injection showed a moderate metabolism rate, and its 24 h-post injection (p.i.) organ distribution was similar to the expression profile in body. Micro-PET imaging of mice after intrapulmonary injection showed high uptake of lung at 1, 4, 24 h p.i.. In conclusion, the experimental results demonstrate the potential of 124 I-RBD as a novel targeted molecular probe for COVID-19. This probe may be used for non-invasive ACE2 mapping in mammals.
研究领域:
放射学
·
分子生物学
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病毒学
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核医学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Qiaoyu He,Yumeng Shi,Hong Xing,Qian Tang,Jing Liu,Chunxia Li,Han Zhang,Boli Zhang,Junhua Zhang,Xiaopeng Chen
Xuanfei Baidu granule (XFBD) is a recommended patented drug for the prevention and treatment of Corona Virus Disease 2019 (COVID-19), which is approved by the National Medical Products Administration. XFBD suppresses the over-activated immune response caused by inflammatory factor storms in COVID-19 infection. The intestine plays a crucial role in the immune system. The mass spectrometry based fecal metabolomics with 16S rDNA sequencing were combined to evaluate the effects of XFBD on host metabolism and gut microbiome. Short-chain fatty acids (SCFAs) contents in fecal matter were quantified by gas chromatography-mass spectrometry (GC-MS). Plasma samples were used to detect immune and inflammatory levels. The results were verified with a rat model of intestinal disorder. Results indicated that XFBD could increase the immune level of Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) ( p < 0.05). The OPLS-DA analysis results showed that a total of 271 differential metabolites (178 up-regulated and 93 down-regulated) were identified based on the VIP ≥1, p < 0.05, FC ≥ 2 and FC ≤ 0.5. The metabolic pathways mainly involved D-Glutamine and D-glutamate metabolism, Arginine biosynthesis, Biotin metabolism, et al. XFBD modified the gut bacteria structure according to the principal component analysis (PCA), that is, 2 phyla, 3 classes, 5 orders, 11 families and 14 genera were significantly different based on taxonomic assignment. In addition, it could partially callback the relative abundance of intestinal microflora in bacterial disorder rats caused by antibiotics. It is suggested that the intervention mechanism of XFBD might be related to the regulation of intestinal flora composition. The evidence obtained in the study provides a useful reference for understanding the mechanism of XFBD.
研究领域:
药理学
·
免疫学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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