Characteristic and quantifiable COVID-19 like abnormalities in CT-  and PET/CT-1 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; Syre,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

Accession Number:

AD1105892

Title:

Characteristic and quantifiable COVID-19 like abnormalities in CT- and PET/CT-1 imaged lungs of SARS-CoV-2 infected crab eating macaques (Macaca fascicularis)

Descriptive Note:

Journal Article - Open Access

Corporate Author:

NATIONAL INST OF ALLERGY AND INFECTIOUS DISEASES FORT DETRICK MD BETHESDA United States

Personal Author(s):

Report Date:

2020-05-14

Pagination or Media Count:

48.0

Abstract:

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-moderateCOVID-19 e.g., ground-glass opacities with or without reticulation, paving, or alveolar consolidation, peri-bronchial thickening, linear opacities at typical locations peripheralcentral, 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. PETCT 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.