# Impacts of SARS-CoV-2 Infection and Age on Musculoskeletal Health

> **NIH NIH F31** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $39,019

## Abstract

PROJECT SUMMARY/ABSTRACT
 The Coronavirus Disease 2019 (COVID-19) pandemic as of June 14, 2021, has totaled 176.02 million
cases, 3.80 million deaths, and 2.37 billion vaccine doses have been administered globally. However, many
have suffered prior to the vaccine and have survived or will still suffer without the vaccine. Therefore,
determining the possible long-term health ramifications post-infection, how they vary based on age at the time
of infection, and whether disease severity differentially impacts long-term health is imperative. Information on
how COVID-19 affects bone metabolism and homeostasis is limited. This is of crucial concern because the
aging population generally has higher bone loss and are at the highest risk of developing severe COVID-19
infection. The objective of the current application is to determine whether long-term deficits in bone mass
are experienced following SARS-CoV-2 infection. The long-term goal is to develop potential treatment
strategies to combat COVID-19 related bone loss. Preliminary studies showed that in a K18-hACE2 mouse
model of COVID-19, surviving mice infected with 1x103 or 1x104 PFU exhibited up to a 24% reduction in
trabecular bone volume fraction just 2 weeks post infection (p<0.001). Infected mice had a 63% increase in
osteoclast numbers (p<0.0002) and a 30% increase in surface occupied by osteoclasts (p<0.02) compared to
non-infected controls. Additionally, mice infected with any dose of SARS-CoV-2 had a 40% increase in
megakaryocytes (MKs) within their femoral bone marrow compared to that observed in mock-infected controls
(p<0.008). Further, previously conducted studies showed that MKs regulate bone mass and osteoclast (OC)
formation (aged MKs increase OCs and have increased RANKL expression). Moreover, patients with severe
forms of COVID-19 have upregulated expression of numerous cytokines and growth factors which is known as
an inflammatory cytokine storm. Many of these cytokines, including IL-6 and TNF-α, are known to regulate
OCs and/or MKs and may be responsible for the bone loss observed in the preliminary studies. Based on
these observations it is hypothesized that i) SARS-CoV-2 infection results in long-term health complications in
the musculoskeletal system, and ii) SARS-CoV-2 infection and the associated cytokine storm increases MK-
stimulated OC formation. To test this hypothesis, two specific aims will be pursued: 1- determine whether
following SARS-CoV-2 infection the bone loss observed remains over time and whether age at the time of
infection impacts the severity of bone loss induced by SARS-CoV-2 infection, and: 2- investigate the
mechanisms by which OC formation and bone resorption are increased as a consequence of SARS-CoV-2
infection and age, including the extent to which MKs from infected mice induce OC formation and bone
resorption. The successful completion of these studies will deepen the understanding of the health implications
post-infection with SARS-COV-2 and will dem...

## Key facts

- **NIH application ID:** 10465474
- **Project number:** 1F31AG077931-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Olatundun Dupe Awosanya
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,019
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465474

## Citation

> US National Institutes of Health, RePORTER application 10465474, Impacts of SARS-CoV-2 Infection and Age on Musculoskeletal Health (1F31AG077931-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10465474. Licensed CC0.

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