Rapid community-driven development of a SARS-CoV-2 tissue simulator

Yafei Wang; Randy Heiland; Morgan Craig; Courtney L. Davis; Ashlee N Ford Versypt; Adrianne Jenner; Jonathan Ozik; Nicholson Collier; Chase Cockrell; Andrew Becker; Gary An; James A. Glazier; Aarthi Narayanan; Amber M Smith; Paul Macklin

Inflammation, ACE2 binding, and host response data Given the impact of SARS-CoV-2, we anticipate an unprecedented amount of mechanistic data to emerge from both clinical and preclinical sources. Of particular value in testing and refining the model will be randomized controlled interventional trials in general or specific populations. As of March, 30 2020, there were 119 trials registered at clinicaltrial.gov under the search term "COVID-19+Drug". Within this 119, there are multiple interventions at different points of the pathophysiology, including, but not limited to: hyperimmune plasma, IL-6 Antibody (e.g. Tocilizumab), protease inhibitors (e.g. Lopinavir/ritonavir), cloroquine/hydroxychloroquine, and Janus Kinases inhibitors (e.g. Baricitinib). As this platform develops, we anticipate predicting the responses to such therapies and refining the model with emerging data such that the range of clinical responses are captured with adequate fidelity. Additionally, data collected from patients or animals during infection, including the presence of various immune cell subsets in lung tissue and systemic markers of inflammation, will serve to differentiate responses to SARS-CoV-2. These data will be similarly integrated to calibrate and validate the model to ensure accurate predictions of therapeutic outcomes based on clinical characteristics.