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Successful recovery of COVID-19-associated recurrent diarrhea and gastrointestinal hemorrhage using convalescent plasma

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Military Medical Research 2021年第1期8卷 132-137页

作者： Li-Bo Zhang Rong-Rong Pang Qing-Hua Qiao Zhi-Hua Wang Xin-Yi Xia Chang-Jun Wang Xiao-Li Xu COVID-19 Research Center Institute of Laboratory MedicineJinling HospitalNanjing University School of Medicinethe First School of Clinical MedicineSouthern Medical UniversityNanjing 210002JiangsuChina Department of laboratory medicine Nanjing Red Cross Blood CenterNanjing 210003JiangsuChina Medical and Technical Support Department Pingdingshan Medical Districtthe 989th HospitalPingdingshan 467000HenanChina Department of laboratory medicine&blood transfusion Wuhan Huoshenshan HospitalWuhan 430100HubeiChina Department of laboratory medicine&blood transfusion the 907th HospitalNanping 350702FujianChina Joint Expert Group for COVID-19 Wuhan Huoshenshan HospitalWuhan 430100HubeiChina Center for Disease Control and Prevention of PLA No.20 Dongda StreetFengtai DistrictBeijing 100071China Department of Medical Administration Jinling HospitalNanjing University School of MedicineNo.305 East Zhongshan RoadNanjing 210002JiangsuChina

Background: Gastrointestinal symptoms are not rare among coronavirus disease 2019(COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients.Case presentation: We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration.Conclusion: When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.

关键词： Coronavirus disease 2019(COVID-19) Convalescent plasma SARS-Co V-2 virus Gastrointestinal symptoms

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Development of a PDRA Method for Detection of the D614G Mutation in COVID-19 virus—Worldwide,2021

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China CDC weekly 2021年第21期3卷 448-453页

作者： Ziwei Chen Xinxin Shen Ji Wang Xiang Zhao Yuan Gao Ruiqin Zhang Jinrong Wang Leping Liu Xinmin Nie Xuejun Ma Department of laboratory medicine Third Xiangya HospitalCentral South UniversityChangshaHunanChina Department of NHC Key laboratory of Medical Virology and Viral Diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Department of blood transfusion Third Xiangya HospitalCentral South UniversityChangshaHunanChina Center for Biosafety Mega-Science Chinese Academy of SciencesWuhanHubeiChina.

ABSTRACT Background:COVID-19 infection is a major public health problem worldwide,and the D614G mutation enhances the infectivity of COVID-19.Methods:A probe-directed recombinase amplification(PDRA)assay was discussed to detect the D614G mutation at 39℃for 30 min.The sensitivity,specificity,and reproducibility of the PDRA were evaluated by D614 and G614 recombinant plasmids.The clinical performance of PDRA assay was validated by testing of 53 previously confirmed COVID-19 positive RNAs and 10 negative samples.Direct sequencing was carried out in parallel for comparison.Result:With good reproducibility and specificity,the PDRA assay worked well with the concentration in the range of 103–107 copies/reaction.Compared with direct sequencing as a reference,the recombinase-aided amplification(RAA)assay obtained 100%sensitivity and 100%specificity using clinical samples.

关键词： specificity PDR D61

Pathological features of COVID-19-associated lung injury:a preliminary proteomics report based on clinical samples

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Signal Transduction and Targeted Therapy 2020年第1期5卷 448-456页

作者： Ling Leng Ruiyuan Cao Jie Ma Danlei Mou Yunping Zhu Wei Li Luye Lv Dunqin Gao Shikun Zhang Feng Gong Lei Zhao Bintao Qiu Haiping Xiang Zhongjie Hu Yingmei Feng Yan Dai Jiang Zhao Zhihong Wu Hongjun Li Wu Zhong Stem Cell and Regenerative medicine Lab Department of Medical Science Research CenterTranslational Medicine CenterPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical Sciences100730 BeijingChina National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and Toxicology100850 BeijingChina State Key laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of Life Omics102206 BeijingChina Department of Infectious Diseases Beijing YouAn HospitalCapital Medical University100069 BeijingChina institute of NBC Defense 102205 BeijingChina Department of Stem Cell and Regenerative medicine laboratory Institute of Health Service and Transfusion Medicine100850 BeijingChina Department of Radiology Beijing YouAn HospitalCapital Medical of University100069 BeijingChina beijing YouAn Hospital Capital Medical University100069 BeijingChina Department of Respiratory and Critical Care medicine Nanyang Central Hospital473000 HenanChina

The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality.However,the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown.To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach,fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia.After virus inactivation,a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues.We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism,blood coagulation,immune response,angiogenesis,and cell microenvironment regulation.Several inflammatory factors were upregulated,which was possibly caused by the activation of NF-κB signaling.Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered.Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection,and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.

关键词： lung metabolism mortality

Flavivirus-infected hosts attract more mosquitoes to bite

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Frontiers of medicine 2023年第2期17卷 355-357页

作者： Hong Zhang Xi Yu Yibin Zhu Gong Cheng Tsinghua University-Peking University Joint Center for Life Sciences School of MedicineTsinghua UniversityBeijing 100084China institute of Infectious Diseases Shenzhen Bay LaboratoryShenzhen 518000China

Mosquitoes adapt to different habitats and feed on a variety of animals.Anthropophilic female mosquitoes,such as Aedes aegypti and Anopheles gambiae,have a strong innate drive to detect their human hosts and acquire blood meals for their egg production[1].Their biting behavior is not only annoying but also transmits many life-threatening diseases.Aedes aegypti has evolved to specialize in biting humans and is the vector of many mosquito-borne diseases,such as dengue virus(DENV),Zika virus(ZIKV),yellow fever virus(YFV),and chikungunya virus(CHIKV)[2].Anopheles gambiae,the malaria vector,has also developed a preference for humans,which makes it an effective vector for disease transmission.Many mosquito-borne infectious diseases pose an increasing global health threat,and consequently,there is an urgent need to control their transmission.

关键词： diseases infected yellow

The efficacy assessment of convalescent plasma therapy for COVID-19 patients:a multi-center case series

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Signal Transduction and Targeted Therapy 2020年第1期5卷 651-662页

作者： Hao Zeng Dongfang Wang Jingmin Nie Haoyu Liang Jiang Gu Anne Zhao Lixin Xu Chunhui Lang Xiaoping Cui Xiaolan Guo Changlong Zhou Haibo Li Bin Guo Jinyong Zhang Qiang Wang Li Fang Wen Liu Yishan Huang Wei Mao Yaokai Chen Quanming Zou National Engineering Research Center of Immunological Department of Microbiology and Biochemical PharmacyCollege of Pharmacy and Laboratory MedicineThird Military Medical UniversityChongqingP.R.China State Key laboratory of Trauma Burn and Combined InjuryThird Military Medical UniversityChongqingP.R.China institute of blood transfusion Chongqing Blood CenterChongqingP.R.China Chongqing Public Health Medical Central ChongqingP.R.China Division of HIV/AIDS and Sex-transmitted virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug ControlBeijingP.R.China Chongqing University Three Gorges Hospital&Chongqing Three Gorges Central Hospital ChongqingP.R.China Affiliated Hospital of North Sichuan Medical College NanchongP.R.China Yongchuan Hospital of Chongqing Medical University ChongqingP.R.China

Convalescent plasma(CP)transfusion has been indicated as a promising therapy in the treatment for other emerging viral infections.However,the quality control of CP and individual variation in patients in different studies make it rather difficult to evaluate the efficacy and risk of CP therapy for coronavirus disease 2019(COVID-19).We aimed to explore the potential efficacy of CP therapy,and to assess the possible factors associated with its efficacy.We enrolled eight critical or severe COVID-19 patients from four centers.Each patient was transfused with 200–400mL of CP from seven recovered donors.The primary indicators for clinical efficacy assessment were the changes of clinical symptoms,laboratory parameters,and radiological image after CP transfusion.CP donors had a wide range of antibody levels measured by serology tests which were to some degree correlated with the neutralizing antibody(NAb)level.No adverse events were observed during and after CP transfusion.Following CP transfusion,six out of eight patients showed improved oxygen support status;chest CT indicated varying degrees of absorption of pulmonary lesions in six patients within 8 days;the viral load was decreased to a negative level in five patients who had the previous viremia;other laboratory parameters also tended to improve,including increased lymphocyte counts,decreased C-reactive protein,procalcitonin,and indicators for liver function.The clinical efficacy might be associated with CP transfusion time,transfused dose,and the NAb levels of CP.This study indicated that CP might be a potential therapy for severe patients with COVID-19.

关键词： patients transfusion fused

Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro~1

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Acta Pharmacologica Sinica 2005年第10期26卷 1274-1280页

作者： Shu-jia DAI~2, Gui-fang DOU~3, Xiao-hong QIAN~(4,5), Hai-feng SONG~4, Zhong-ming TANG~2, De-sheng LIU~2, Xiu-wen LIU~2, Liu-meng YANG~6, Yong-tang ZHENG~6, Qing LIANG~7 ~2 laboratory of Metabolism of Biotechnology Derived Drugs, beijing institute of Radiation medicine, beijing 100850 ~3 laboratory of Drug Metabolism and Pharmacokinetics, beijing institute of transfusion medicine, beijing 100850 ~5 Laboratories of Genomics and Proteomics, beijing institute of Radiation medicine, beijing 100850 ~6 laboratory of Molecular hnmunopharmacology, Kunming institute of Zoology, Chinese Academy of Sciences, Kunming 650223 ~7 FusoGen Pharmaceuticals Inc, Tianjin 300051, China laboratoryofMetabolismofBiotechnologyDerivedDrugs BeijingInstituteofRadiationMedicineBeijing100850 laboratoryofDrugMetabolismandPharmacokinetics BeijingInstituteofTransfusionMedicineBeijing100850

Aim: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. Methods: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry (SPELC/MS/MS) was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-127I iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC50) of sifuvirtide on cell fusion was determined by co-cultivation assay. Results: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000μg/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10 626±2 886μg/L and 528±191μg/L, and the terminal imination half-lives (T1/2) were 6.3±0.9 h and 5.5±1.0 h, respectively. After sc, Tmaxwas 0.25-2h, and the absolute bioavailability was 49%±13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC50of 0.33μg/L. Conclusion: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T1/2of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC50in vitro.

关键词： sifuvirtide pharmacokinetics HIV HIV fusion inhibitors enfuvirtide on-line solid-phase extraction macaque

Chemical Synthesis of Peptide Antigens From Nucleocapsid Protein of Hepatitis C virus and Their Application to Serodiagnosis of Viral Infection

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Progress in Natural Science:Materials International 1994年第3期 114-119页

作者：金冬雁薛水星杨永平李景源吴长龙刘崇柏李玉英侯云德 beijing 100052 Chinese Academy of Preventive medicine institute of Virology PRC Shanghai Instrtute of Biological Products State Key laboratory of Molecular Virology and Genetic Engineering

Hepatitis C virus (HCV) contains a positite- and single-stranded RNA genomeand was proposed in 1991 to be placed in the new third genus of the familyFlaviviridae. Sufficient data obtained all around the world indicate that about 90%of post-transfusion hepatitis is caused by HCV and that chronic HCV infection can in-crease the risk of the development of primary hepatocellular carcinoma. In thepreliminary epidemiological investigations, a high prevalence of anti-HCV antibodieswas detected in Chinese patients with liver disease and Chinese occupational blood do-nors, especially the plasmapheresis donors. That is to say, HCV causes a serioushealth problem in China and diagnostic assays for HCV infection are in urgent need

关键词： hepatitis C virus (HCV) synthetic peptide ELLSA.

Genetic mechanisms of critical illness in Covid-19

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四川生理科学杂志 2020年第4期42卷 455-455页

作者： Erola Pairo-Castineira Roslin institute University of Edinburgh Edinburgh UK MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK Genomics England London UK Centre for Inflammation Research The Queen’s Medical Research Institute University of Edinburgh Edinburgh UK Centre for Genomic and Experimental medicine Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK Edinburgh Clinical Research Facility Western General Hospital University of Edinburgh Edinburgh UK Intensive Care National Audit & Research Centre London UK institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia Biostatistics Group School of Life Sciences Sun Yat-sen University Guangzhou China The Crick institute London UK Intensive Care Unit Royal Infirmary of Edinburgh Edinburgh UK School of Life Sciences Westlake University Hangzhou China Westlake laboratory of Life Sciences and Biomedicine Hangzhou China Wellcome Centre for Human Genetics University of Oxford Oxford UK Department of medicine University of Cambridge Cambridge UK Department of Intensive Care medicine Guy’s and St Thomas’ NHS Foundation Trust London UK School of Immunology and Microbial Sciences King’s College London London UK NIHR Health Protection Research Unit for Emerging and Zoonotic Infections Institute of Infection Veterinary and Ecological Sciences University of Liverpool Liverpool UK MRC-University of Glasgow Centre for virus Research Institute of Infection Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow Glasgow UK William Harvey Research institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK Centre for Tropical medicine and Global Health Nuffield Department of Medicine University of Oxford Oxford UK Clinical Research Centre at St Vincent’s University Hospital Un

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19.Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC(Genetics Of Mortality In Critical Care)genome-wide association study(GWAS)in 2244 critically ill Covid-19 patients from 208 UK intensive care units(ICUs).We identify and replicate novel genome-wide significant associations,on chr12q24.13(rs10735079,p=1.65[Formula:see text]10-8)in a gene cluster encoding antiviral restriction enzyme activators(OAS1,OAS2,OAS3),on chr19p13.2(rs2109069,p=2.3[Formula:see text]10-12)near the gene encoding tyrosine kinase 2(TYK2),on chr19p13.3(rs2109069,p=3.98[Formula:see text]10-12)within the gene encoding dipeptidyl peptidase 9(DPP9),and on chr21q22.1(rs2236757,p=4.99[Formula:see text]10-8)in the interferon receptor gene IFNAR2.We identify potential targets for repurposing of licensed medications:using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2,and high expression of TYK2,to life-threatening disease;transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19.Our results identify robust genetic signals relating to key host antiviral defence mechanisms,and mediators of inflammatory organ damage in Covid-19.Both mechanisms may be amenable to targeted treatment with existing drugs.Large-scale randomised clinical trials will be essential before any change to clinical practice.

关键词： lung drugs critical

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