Development of a rapid multiplex CRISPR-based testing pathway for tuberculosis and COVID-19

开发基于 CRISPR 的结核病和 COVID-19 快速多重检测途径

• 批准号: 10432930
• 负责人: Padmapriya Banada
• 金额: $ 24.49万
• 依托单位: RBHS-NEW JERSEY MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-12 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10432930
• 关键词: 2019-nCoV; Africa South of the Sahara; Asia; Biological Assay; COVID-19; COVID-19 assay; COVID-19 diagnostic; COVID-19 impact; COVID-19 mortality; COVID-19 patient; Cause of Death; Cessation of life; Chemicals; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Communicable Diseases; DNA; Detection; Development; Diagnostic; Eastern Europe; Evaluation; Future; Health Resources; Healthcare Systems; Individual; Infection; Methods; Morbidity - disease rate; Mycobacterium tuberculosis; Nucleic Acids; Oral; Pathway interactions; Patients; Performance; Phase; Population; Prevalence; Property; Protocols documentation; Public Health; RNA; Rapid screening; Research Personnel; Resource-limited setting; Resources; Risk Factors; SARS-CoV-2 infection; Saliva; Sampling; Signs and Symptoms; South America; Specimen; Sputum; Stress; Swab; Symptoms; Technical Expertise; Technology; Testing; Tuberculosis; Validation; Work; base; case finding; cost; detection limit; diagnostic platform; mortality; novel; pandemic disease; pathogen; point of care; prototype; rapid technique; respiratory; respiratory pathogen; saliva sample; screening; transmission process; tuberculosis diagnostics

PROJECT ABSTRACT Tuberculosis (TB) and COVID-19 (COVID) are currently the deadliest pathogens worldwide, with 1.4 million TB and 2.5 million COVID deaths annually, both perpetuated by potential transmission from undiagnosed, asymptomatic infection. In the many TB-COVID co-endemic populations in Asia, sub-Saharan Africa, South America, and Eastern Europe, there is a critical need for widespread, active, symptom-agnostic screening of TB and COVID to control transmission and reduce morbidity and mortality. However, the simultaneous burden of COVID and TB poses enormous stress on these health care systems with severely limited bandwidth and resources for active case finding and surveillance. Consequently, around 400 thousand more TB deaths are estimated in the next 5 years compared to prior years as a direct consequence of COVID. Beyond their global co-prevalence and potential for asymptomatic transmission, TB and COVID’s overlapping clinical signs and symptoms, risk factors, and shared respiratory transmission pathways allow for a combined rapid screening approach that can detect both infections using one sample and testing pathway. This would enable i) more wide-spread screening, ii) at higher efficiency – fewer individuals need to be screened to detect one TB or COVID infected individual. We propose to leverage our existing TB and COVID non-invasive samples (eg. sputum, concentrated saliva, oral swabs), common processing methods and a novel point-of-care compatible CRISPR-Cas 13 COVID diagnostic system (SHINE) to pilot a streamlined approach to simultaneously screen for TB and COVID. Specifically, to develop this combined screening strategy, we will pursue the following aims: 1) transition a point-of-care CRISPR platform for multiplex screening of TB and COVID, and 2) optimize co-extraction methods from TB and COVID sputum and sputum specimens. These complementary aims will contribute independent value to enable streamlined testing and control of both COVID and TB, and are adaptable towards rapid, multiplex screening and surveillance of future pandemics.

项目摘要 结核病（TB）和新冠肺炎（COVID-19）是目前全球最致命的病原体， 每年有 140 万人死于结核病，250 万人死于新冠肺炎，两者均因潜在传播而持续存在 来自未确诊的无症状感染者。 亚洲、撒哈拉以南非洲、南美洲和东欧，迫切需要 对结核病和新冠病毒进行广泛、积极、与症状无关的筛查，以控制传播和 降低发病率和死亡率 然而，新冠肺炎和结核病同时造成负担。 带宽和资源严重有限，给这些医疗保健系统带来巨大压力 通过积极的病例发现和监测测试，结核病死亡人数增加了约 40 万人。 与前几年相比，预计未来 5 年的损失是新冠疫情的直接后果。 除了全球共同流行和无症状传播的潜力之外，结核病和新冠病毒 重叠的临床体征和症状、危险因素和共同的呼吸道传播 允许组合快速筛查方法的途径，该方法可以使用以下方法检测这两种感染 单一样本和测试途径将实现 i) 更广泛的筛查，ii) 更高的水平。 效率——需要筛查即可发现结核病或新冠病毒感染者的人数更少。 我们建议利用我们现有的结核病和新冠病毒非侵入性样本（例如痰液、 浓缩唾液、口腔拭子）、常见处理方法和新颖的护理点 兼容的 CRISPR-Cas 13 COVID 诊断系统 (SHINE) 试点简化方法 同时筛查结核病和新冠肺炎，具体来说是开发这种联合筛查。 根据战略，我们将追求以下目标：1）将 CRISPR 平台转变为 结核病和新冠病毒的多重筛查，以及 2) 优化结核病和新冠病毒的共提取方法 这些互补的目标将为痰和痰标本贡献独立的价值。 能够简化新冠肺炎和结核病的检测和控制，并且能够适应快速、 对未来流行病的多重筛查和监测。