Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa

对东南亚和西非/中非具有大流行潜力的病毒的传播、适应和发病机制进行区域间研究

• 批准号: 10426422
• 负责人: Anavaj SAKUNTABHAI
• 金额: $ 45.45万
• 依托单位: INSTITUT PASTEUR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-31 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426422
• 关键词: 2019-nCoV; Acute; Africa; African; Area; Blood Circulation; Burkina Faso; COVID-19; COVID-19 patient; COVID-19 surveillance; COVID-19 vaccination; Cambodia; Cameroon; Centers for Disease Control and Prevention (U.S.); Central Africa; Cessation of life; Clinical; Communities; Coronavirus; Country; Data; Data Collection; Detection; Developed Countries; Disease; Disease Outbreaks; Disease Surveillance; Dose; Ensure; Epidemiology; Equatorial Guinea; Event; Far East; Gambia; Genetic Determinism; Genomics; Goals; Guinea; Guinea-Bissau; Health system; Incidence; Income; Ivory Coast; Knowledge; Laboratories; Laos; Madagascar; Mali; Mauritania; Medicine; Metadata; Methods; Molecular; Monitor; Niger; Patients; Population; Recording of previous events; Reporting; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2 B.1.1.7; SARS-CoV-2 B.1.351; SARS-CoV-2 B.1.617.2; Sampling; Senegal; Severities; Severity of illness; Societies; Source; Southeastern Asia; Symptoms; System; Thailand; Time; Timidity; Tunisia; Vaccinated; Vaccination; Vaccines; Variant; Vietnam; Viral Pathogenesis; Virus; base; detection method; genetic signature; genome sequencing; genomic data; molecular subtypes; pandemic disease; pathogen genomics; respiratory; response; sequencing platform; severe COVID-19; stem; tool; transmission process; variants of concern; virus genetics; whole genome

Project Summary/Abstract Severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) has rapidly spread across the world. As of June, 2021, over 171 million laboratory-confirmed cases and greater than 3.68 million deaths have been reported globally. This increase in cases has been associated with emergence of new variants which have increased transmissibility and severity. While Southeast Asia kept COVID-19 cases under relative control in 2020. In 2021, SARS-CoV-2 began to spread rapidly and caused continuing outbreaks in the region. In Africa, the genomic surveillance gap, combined with very fragile health systems with limited management capacities, exposes the continent to possible new COVID-19 waves that could prove to be much more severe on the continent, where vaccination clearly remains at a very timid stage. The overall goal of the project is to increase sequencing capacity and add to the depth of sequencing knowledge available in South East Asia and African countries with 4 Specific Aims. 1)To increase sequencing numbers for samples from certain regions. We will focus on samples from land borders with Thailand and Vietnam and community transmission in Cambodia stemming from the February 20th “event.” These sequences will help to understand community transmission within Cambodia. In Africa, we will increase sequencing numbers from samples from African countries with very low sequencing coverage including Mali, Burkina Faso, Guinea, Côte d’Ivoire, Guinea-Bissau, Niger, Cabo-Verde, Mauritania, Tunisia, Madagascar, Cameroon, Equatorial Guinea and Central Africa Republic. We will confirm known variants of concern as well as detection of potential local new variants. 2)To increase sequencing numbers for samples from patients with atypical profiles. We will systematically collect data at epidemiological level for demographical data, clinical symptoms, COVID-19 vaccination status, history of COVID-19 in relation with patients. We will focus on re-infected patient samples, severe COVID-19 cases and post-vaccinated SARS-CoV-2 infected patients. 3) To monitor introduction and dissemination of known VOCs using molecular sub-typing tools. We will help participating countries building up molecular capacities to subtype known variants. 4) Identify viral genetic determinants of high transmissibility and disease severity. Sequences from severe cases will be analyzed in comparison to the sequences from the randomly selected group to identify viral genetic signatures associated to disease severity. Regarding the transmissibility, we will rely on circulation dynamics of the detected variants in each country as well as in all countries. Overall, the studies outlined in this proposal will rapidly add essential sequence data needed regarding COVID-19 cases in lower–middle income, least-developed countries. They will provide the basis for further study on inter-/intra-host variant emergence and vaccine escape in a unique population from a least-developed country in an understudied, but vitally important, region of the world.

项目总结/摘要 严重急性呼吸道冠状病毒2（SARS-CoV-2），2019冠状病毒病的病原体 （COVID-19）已迅速在全球蔓延。截至2021年6月，超过1.71亿例实验室确认的 全球报告的病例和死亡人数超过368万。病例的增加是 与新变异的出现相关，这些变异具有增加的传播性和严重性。而 2020年，东南亚地区的COVID-19病例得到了相对控制。2021年，SARS-CoV-2开始传播 并在该地区造成持续的疫情。在非洲，基因组监测缺口， 非洲大陆的卫生系统非常脆弱，管理能力有限， COVID-19在非洲大陆可能会被证明更为严重，因为疫苗接种显然 仍然处于非常谨慎的阶段。该项目的总体目标是增加测序能力， 东南亚和非洲国家测序知识的深度，有4个具体目标。 1）增加来自某些地区的样品的测序数量。我们将重点关注来自 与泰国和越南接壤的陆地边界，以及柬埔寨的社区传播， 2月20日“事件”。这些序列将有助于了解柬埔寨境内的社区传播。 在非洲，我们将增加来自非洲国家的样本的测序数量， 覆盖范围包括马里、布基纳法索、几内亚、科特迪瓦、几内亚比绍、尼日尔、佛得角、 毛里塔尼亚、突尼斯、马达加斯加、喀麦隆、赤道几内亚和中非共和国。我们将确认 已知的相关变体以及潜在的本地新变体的检测。（2）增加排序 来自具有非典型特征的患者的样本的数量。我们将系统地收集数据， 人口统计学数据、临床症状、COVID-19疫苗接种状况、 COVID-19与患者的关系。我们将重点关注再感染患者样本、严重COVID-19病例 和接种后的SARS-CoV-2感染患者。3)监测采用和传播 已知的挥发性有机化合物使用分子分型工具。我们将帮助参与国建立分子 对已知变体进行分型的能力。4)确定高传播性的病毒遗传决定因素， 疾病严重程度。将对来自严重病例的序列与来自 随机选择一组，以确定与疾病严重程度相关的病毒遗传特征。关于 传播性，我们将依赖于每个国家以及所有国家检测到的变体的流通动态。 国家总的来说，本提案中概述的研究将迅速增加所需的基本序列数据， 关于中低收入、最不发达国家的COVID-19病例。他们将提供基础 为了进一步研究在一个独特的人群中宿主间/宿主内变异的出现和疫苗逃逸， 在世界上一个未被充分研究，但至关重要的地区，最不发达国家。