|Poster Title:||SARS-CoV-2 Infection in Mice Causes Trabecular Bone Loss Through Increased Osteoclast Numbers|
|Authors:||Christopher E. Dalloul, Olatundun D. Awosanya, Ushashi C. Dadwal, Rachel J. Blosser, Nicholas Hux, Abduallah G. Elsayed, Nikhil P. Tewari, Samuel Zike, Rebekah J. Addison, Mikayla R. Stevens, Austyn Colter, Joydeep Ghosh, Mariel Carozza, Michael J. Klemsz, Nancy A. Johnston, Edward F. Srour, George E. Sandusky, Melissa A. Kacena1,|
There are dangerous knowledge gaps regarding the consequences of infection by SARS-CoV-2 on the musculoskeletal system. This pilot study examined fundamental bone health parameters among increasing viral loads.
Thirty-seven male C57BL/6 (WT) and K18-hACE2 transgenic mice expressing human ACE2 (TG) were split into eight groups (n=4-6/group) and subjected to intranasal dosing of 0, 1×103, 1×104, 1×105 PFU of SARS-CoV-2. Upon death or study endpoint (12-14 days post-infection (dpi)), femurs were collected for µCT and histological analysis.
We report here that all WT (mock and infected) mice survived and were healthy until termination of the study, while all 1×105 PFU TG mice died 6-7 dpi, validating the SARS-CoV-2 TG mouse model. With one exception, TG mice receiving 1×103 PFU appeared healthy throughout the entire experiment. Similarly, TG mice receiving 1×104 PFU had two early deaths; the remainder were unhealthy but then recovered and were indistinguishable from WT mice by study endpoint. No difference was found in µCT-determined bone parameters among the WT groups. There was a 22% decrease in trabecular bone volume fraction (p<0.0004), 18% increase in trabecular separation (p<0.002), 27% decrease in trabecular number (p<0.006), and a trending 12% reduction in trabecular thickness (p=0.07) among TG mice receiving any amount of virus compared to mock-infected controls. Infected mice had a 63% increase in osteoclast numbers (p<0.0002) and a 30% increase in surface occupied by osteoclasts (p<0.02).
While more studies are needed to investigate the long-term consequences of its musculoskeletal effects, this study demonstrates a significant alteration from SARS-CoV-2 in asymptomatic, moderate, and severely infected mice.
Translational/Human Health Impact:
TG mice infected with these viral loads may serve as models for COVID-19 patients with varying degrees of severity. These results urge clinicians to closely monitor the bone health of current and recovered COVID-19 patients.