Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis)

Finch, Courtney L.; Crozier, Ian; Lee, Ji Hyun; Byrum, Russ; Cooper, Timothy K.; Liang, Janie; Sharer, Kaleb; Solomon, Jeffrey; Sayre, Philip J.; Kocher, Gregory; Bartos, Christopher; Aiosa, Nina M.; Castro, Marcelo; Larson, Peter A.; Adams, Ricky; Beitzel, Brett; Di Paola, Nicholas; Kugelman, Jeffrey R.; Kurtz, Jonathan R.; Burdette, Tracey; Nason, Martha C.; Feuerstein, Irwin M.; Palacios, Gustavo; Claire, Marisa C. St.; Lackemeyer, Matthew G.; Johnson, Reed F.; Braun, Katarina M.; Ramuta, Mitchell D.; Wada, Jiro; Schmaljohn, Connie S.; Friedrich, Thomas C.; O’Connor, David H.; Kuhn, Jens H.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing an exponentially increasing number of coronavirus disease 19 (COVID-19) cases globally. Prioritization of medical countermeasures for evaluation in randomized clinical trials is critically hindered by the lack of COVID-19 animal models that enable accurate, quantifiable, and reproducible measurement of COVID-19 pulmonary disease free from observer bias. We first used serial computed tomography (CT) to demonstrate that bilateral intrabronchial instillation of SARS-CoV-2 into crab-eating macaques (Macaca fascicularis) results in mild-to-moderate lung abnormalities qualitatively characteristic of subclinical or mild-to-moderate COVID-19 (e.g., ground-glass opacities with or without reticulation, paving, or alveolar consolidation, peri-bronchial thickening, linear opacities) at typical locations (peripheral>central, posterior and dependent, bilateral, multi-lobar). We then used positron emission tomography (PET) analysis to demonstrate increased FDG uptake in the CT-defined lung abnormalities and regional lymph nodes. PET/CT imaging findings appeared in all macaques as early as 2 days post-exposure, variably progressed, and subsequently resolved by 6–12 days post-exposure. Finally, we applied operator-independent, semi-automatic quantification of the volume and radiodensity of CT abnormalities as a possible primary endpoint for immediate and objective efficacy testing of candidate medical countermeasures.