Animal Model Prescreening: Pre-exposure to SARS-CoV-2 impacts responses in the NHP model

Ricks, Keersten M.; Herbert, Andrew S.; Koehler, Jeffrey W.; Kuehnert, Paul A.; Clements, Tamara L.; Shoemaker, Charles J.; Kuehne, Ana I.; O’Brien, Cecilia M.; Coyne, Susan R.; Delp, Korey L.; Akers, Kristen S.; Dye, John M.; Hooper, Jay W.; Smith, Jeffrey M.; Kugelman, Jeffrey R.; Beitzel, Brett F.; Gibson, Kathleen M.; Johnston, Sara C.; Minogue, Timothy D.

COVID-19 presents herculean challenges to research and scientific communities for producing diagnostic and treatment solutions. Any return to normalcy requires rapid development of countermeasures, with animal models serving as a critical tool in testing vaccines and therapeutics. Animal disease status and potential COVID-19 exposure prior to study execution may severely bias efficacy testing. We developed a toolbox of immunological and molecular tests to monitor countermeasure impact on disease outcome and evaluate pre-challenge COVID-19 status. Assay application showed critical necessity for animal pre-screening. Specifically, real-time PCR results documented pre-exposure of an African Green Monkey prior to SARS-CoV-2 challenge with sequence confirmation as a community-acquired exposure. Longitudinal monitoring of nasopharyngeal swabs and serum showed pre-exposure impacted both viral disease course and resulting immunological response. This study demonstrates utility in a comprehensive pre-screening strategy for animal models, which captured the first documented case of community-acquired, non-human primate infection. One Sentence Summary Pre-exposure to SARS-CoV-2 affects biomarker responses in animal models, highlighting a need for robust pre-screening protocols prior to medical countermeasure studies.