Pathogenesis, Treatment and Prevention of Emerging Infectious Diseases

新发传染病的发病机制、治疗和预防

• 批准号: 10927791
• 负责人: H. Clifford Lane
• 金额: $ 12万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10927791
• 关键词: 2019-nCoV; Anthrax Attack; Anthrax disease; Antibodies; Antigens; Anxiety Disorders; Area; Autoimmunity; Biological Markers; COVID-19; COVID-19 survivors; COVID-19 therapeutics; COVID-19 treatment; Characteristics; Clinical Trials; Conduct Clinical Trials; Democratic Republic of the Congo; Diagnostic; Diagnostic tests; Disease; Ebola Hemorrhagic Fever; Ebola virus; Emerging Communicable Diseases; Enrollment; Evaluation; Event; Hospitalization; Immune; Immunoglobulins; Influenza; Inhalation; Investigational Therapies; Longitudinal Studies; Longterm Follow-up; Molecular; Monkeypox; Monoclonal Antibodies; Nucleocapsid; Participant; Pathogenesis; Patients; Physical Examination; Plasma; Post-Acute Sequelae of SARS-CoV-2 Infection; Prevention; Recording of previous events; Recovery; Reporting; Research; Respiratory Tract Infections; Risk; Role; SARS-CoV-2 antibody; SARS-CoV-2 infection; SARS-CoV-2 spike protein; Safety; Severe Acute Respiratory Syndrome; Survivors; Symptoms; Therapeutic Trials; Time; Vaccines; Virus Diseases; Woman; arm; cohort; immune activation; improved; long term consequences of COVID-19; long-term sequelae; new pandemic; novel strategies; placebo controlled study; primary endpoint; randomized placebo controlled trial; secondary endpoint; treatment response; volunteer

Research in this project is currently focused on six areas. These are: characterization of the survivors of the anthrax attacks of 2001; characterization of emerging respiratory infections including SARS, COVID-19, and influenza; evaluation of experimental vaccines and treatments for Ebola virus; characterizing the long-term sequelae of Ebola virus infection; evaluating experimental therapeutics for COVID-19; characterizing the long-term sequelae of SARS-CoV-2 infection. The anthrax study has enrolled a cohort of volunteers who are currently undergoing an extensive diagnostic evaluation. The COVID-19 therapeutic trial ACTIV-3, followed its placebo-controlled study of bamlanivimab (a monoclonal antibody directed toward the spike protein of SARS CoV-2) with studies of the Brii monoclonal antibody cocktail (amubarvimab-romlusevimab), the Vir antibody sotrovimab, the Astra-Zeneca combination of antibodies (tixagevimab-cilgavimab) and the Molecular Partners/Novartis darpins (ensovibep). While none of these showed benefit for the primary endpoint of time to recovery, the Astra-Zeneca arm showed an overall improvement in survival in a secondary endpoint. Separating patients into groups based upon baseline levels of antibody to SARS-CoV-2 and plasma levels of SARS-CoV-2 nucleocapsid antigen demonstrated a potential benefit for bamlanivimab in the group that was antibody negative and strongly antigen positive. A randomized, placebo-controlled trial of COVID-19 immune immunoglobulin in hospitalized patients failed to show benefit. A longitudinal study of COVID-19 survivors and controls demonstrated that symptoms consistent with post-acute sequelae of SARS-CoV-2 infection (PASC) were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Abnormal findings on physical examination and diagnostic testing were uncommon. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC.

该项目的研究目前集中在六个领域。 这些是： 2001 年炭疽袭击幸存者的特征；新出现的呼吸道感染的特征，包括 SARS、COVID-19 和流感；埃博拉病毒实验疫苗和治疗方法的评估；描述埃博拉病毒感染的长期后遗症的特征；评估 COVID-19 的实验疗法；描述了 SARS-CoV-2 感染的长期后遗症。 炭疽研究招募了一批志愿者，目前正在进行广泛的诊断评估。 COVID-19 治疗试验 ACTIV-3 紧随其对 bamlanivimab（一种针对 SARS CoV-2 刺突蛋白的单克隆抗体）的安慰剂对照研究以及对 Brii 单克隆抗体混合物（amubarvimab-romlusevimab）（Vir 抗体）的研究sotrovimab、阿斯利康抗体组合 (tixagevimab-cilgavimab) 和 Molecular Partners/Novartis darpins（ensovibep）。 虽然这些都没有显示出对恢复时间的主要终点有好处，但阿斯利康治疗组在次要终点中显示出生存率的总体改善。 根据 SARS-CoV-2 抗体基线水平和 SARS-CoV-2 核衣壳抗原血浆水平将患者分组，证明了 bamlanivimab 在抗体阴性和抗原强阳性组中的潜在益处。 一项针对住院患者的 COVID-19 免疫球蛋白随机、安慰剂对照试验未能显示出疗效。 一项针对 COVID-19 幸存者和对照者的纵向研究表明，55% 的 COVID-19 队列参与者和 13% 的对照参与者报告了与 SARS-CoV-2 感染急性后遗症 (PASC) 一致的症状。女性和有焦虑症病史的人患 PASC 的风险增加。 体检和诊断测试的异常结果并不常见。 探索性研究没有发现 PASC 参与者存在持续病毒感染、自身免疫或异常免疫激活的证据。

项目成果

Mild reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant: First case report from Indonesia.

• DOI: 10.3389/fmed.2022.906469
• 发表时间: 2022
• 期刊: Frontiers in medicine
• 影响因子: 3.9

Living with the COVID-19 pandemic: act now with the tools we have.

• DOI: 10.1016/s0140-6736(20)32117-6
• 发表时间: 2020-10-24
• 期刊: Lancet (London, England)
• 作者: Bedford J;Enria D;Giesecke J;Heymann DL;Ihekweazu C;Kobinger G;Lane HC;Memish ZA;Oh MD;Sall AA;Ungchusak K;Wieler LH;WHO Strategic and Technical Advisory Group for Infectious Hazards
• 通讯作者: WHO Strategic and Technical Advisory Group for Infectious Hazards

A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.

• DOI: 10.1056/nejmoa1414216
• 发表时间: 2017-01-26
• 期刊: The New England journal of medicine
• 作者: Regules JA;Beigel JH;Paolino KM;Voell J;Castellano AR;Hu Z;Muñoz P;Moon JE;Ruck RC;Bennett JW;Twomey PS;Gutiérrez RL;Remich SA;Hack HR;Wisniewski ML;Josleyn MD;Kwilas SA;Van Deusen N;Mbaya OT;Zhou Y;Stanley DA;Jing W;Smith KS;Shi M;Ledgerwood JE;Graham BS;Sullivan NJ;Jagodzinski LL;Peel SA;Alimonti JB;Hooper JW;Silvera PM;Martin BK;Monath TP;Ramsey WJ;Link CJ;Lane HC;Michael NL;Davey RT Jr;Thomas SJ;rVSVΔG-ZEBOV-GP Study Group
• 通讯作者: rVSVΔG-ZEBOV-GP Study Group

Characteristics and Clinical Management of a Cluster of 3 Patients With Ebola Virus Disease, Including the First Domestically Acquired Cases in the United States.

• DOI: 10.7326/m15-0530
• 发表时间: 2015-07-21
• 期刊: Annals of internal medicine
• 影响因子: 39.2
• 作者: Liddell AM;Davey RT Jr;Mehta AK;Varkey JB;Kraft CS;Tseggay GK;Badidi O;Faust AC;Brown KV;Suffredini AF;Barrett K;Wolcott MJ;Marconi VC;Lyon GM 3rd;Weinstein GL;Weinmeister K;Sutton S;Hazbun M;Albariño CG;Reed Z;Cannon D;Ströher U;Feldman M;Ribner BS;Lane HC;Fauci AS;Uyeki TM
• 通讯作者: Uyeki TM

Safety and immunogenicity of multiple and higher doses of an inactivated influenza A/H5N1 vaccine.

• DOI: 10.1086/599992
• 发表时间: 2009-08-15
• 期刊: The Journal of infectious diseases
• 作者: Beigel JH;Voell J;Huang CY;Burbelo PD;Lane HC
• 通讯作者: Lane HC