Interrogating COVID-19, the lung microbiota, and therapeutic phages to mitigate secondary lung infection and inflammation (COVPHA)

The Coronavirus 2019-nCoV pandemic poses a heavy burden on both society and the healthcare system. Similar to other respiratory viruses, the rate of infection with acute bacterial pneumonia in COVID-19 patients is estimated to be up to 16%. To understand the mechanisms of secondary and co-infection in COVID-19 patients and to develop phage-based therapeutics against the associated bacterial pneumonia, we propose COVPHA, which benefits from our recent advances in high-throughput, culture-independent, but host-targeted methods. COVPHA aims to design a whole battery of phage-based therapies that apply multifaceted modes of action against bacterial secondary and coinfections associated with COVID-19 infection. Using an interdisciplinary approach, COVPHA will systematically identify the co-infecting bacteria in COVID19 patients by metagenomics (WP1), and isolate effective phages against target multi-resistant bacteria, using a revolutionary targeted culture-independent method, viral-tagging (WP2). We will determine the efficacy of different phage cocktails against target bacteria (WP 3), via our high-throughput in vitro system. Using tissue culture and in vivo animal models, we will comprehensively investigate the safety and efficacy of selected single phages and phage cocktails against target bacteria (WP4), to lay the foundation for compassionate use and an early clinical trial (WP5).