RT Journal Article SR Electronic T1 Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis) JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.14.096727 DO 10.1101/2020.05.14.096727 A1 Courtney L. Finch A1 Ian Crozier A1 Ji Hyun Lee A1 Russ Byrum A1 Timothy K. Cooper A1 Janie Liang A1 Kaleb Sharer A1 Jeffrey Solomon A1 Philip J. Sayre A1 Gregory Kocher A1 Christopher Bartos A1 Nina M. Aiosa A1 Marcelo Castro A1 Peter A. Larson A1 Ricky Adams A1 Brett Beitzel A1 Nicholas Di Paola A1 Jeffrey R. Kugelman A1 Jonathan R. Kurtz A1 Tracey Burdette A1 Martha C. Nason A1 Irwin M. Feuerstein A1 Gustavo Palacios A1 Marisa C. St. Claire A1 Matthew G. Lackemeyer A1 Reed F. Johnson A1 Katarina M. Braun A1 Mitchell D. Ramuta A1 Jiro Wada A1 Connie S. Schmaljohn A1 Thomas C. Friedrich A1 David H. O’Connor A1 Jens H. Kuhn YR 2020 UL http://biorxiv.org/content/early/2020/05/14/2020.05.14.096727.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.