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

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.