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: 10703869
• 负责人: H. Clifford Lane
• 金额: $ 13.89万
• 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/10703869
• 关键词: 2019-nCoV; Anthrax Attack; Anthrax disease; Antibodies; Antigens; Anxiety Disorders; Area; Autoimmunity; 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; Dose; Ebola Hemorrhagic Fever; Ebola virus; Emerging Communicable Diseases; Enrollment; Evaluation; Event; Immune; Immunoglobulins; Influenza; Infusion procedures; 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; RNA; Randomized; 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; Sampling; Seminal fluid; Severe Acute Respiratory Syndrome; Survivors; Symptoms; Therapeutic Trials; Time; Vaccines; Virus Diseases; Woman; arm; base; cohort; follow-up; immune activation; long term consequences of COVID-19; long-term sequelae; men; novel strategies; pandemic disease; placebo controlled study; primary endpoint; randomized placebo controlled trial; remdesivir; secondary endpoint; viral RNA; 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 Prevail 4 trial enrolled 38 men who had survived Ebola virus infection and had persistent evidence of Ebola virus RNA in their semen and randomized them to receive remdesivir at a dose of 100 mg/d for five days. While no differences in RNA persistence were noted a the end of the infusions; patients randomized to remdesivir had more negative samples in follow-up (96% vs. 81%; p=0.041) 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.

目前，该项目的研究集中在六个领域。 这些是：2001年炭疽袭击的幸存者的表征；包括SARS，COVID-19和流感的新兴呼吸道感染的表征；评估埃博拉病毒的实验疫苗和治疗方法；表征埃博拉病毒感染的长期后遗症；评估COVID-19的实验疗法；表征SARS-COV-2感染的长期后遗症。 炭疽研究已经招募了一群志愿者，他们目前正在接受广泛的诊断评估。 这项盛行的4次试验招募了38名在埃博拉病毒感染中幸存下来的男性，并在精液中持续证明埃博拉病毒RNA，并将其随机分配给他们以100 mg/d的剂量接受五天的剂量。虽然RNA持久性没有差异，但输注的末端是。随机分配给Remdesivir的患者在随访中有更多的负样本（96％vs. 81％； P = 0.041） 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）和分子伙伴/诺华darpins（ensovibep）。 尽管这些都没有显示出恢复时间的主要终点，但Astra-Zeneca臂在次要终点中的生存率总体提高。 根据对SARS-COV-2的基线水平和SARS-COV-2 Nucleocapsid抗原的基线水平将患者分为组，在该组中，Bamlanivimab在抗体阴性和强抗原阳性中对Bamlanivimab的潜在益处。 Covid-19的随机，安慰剂对照试验在住院患者中未能显示出好处。 纵向研究了Covid-19幸存者和对照组，表明55％的Covid-19同类群和13％的对照参与者报道了与SARS-COV-2感染后急性后遗症（PASC）一致的症状。妇女和患有焦虑症病史的女性的风险增加了。 身体检查和诊断测试的异常发现并不常见。 探索性研究没有发现PASC参与者的持续性病毒感染，自身免疫性或异常免疫激活的证据。