The abortive SARS-CoV-2 infection of osteoclast precursors promotes their differentiation into osteoclasts

J Med Virol. 2024 Apr;96(4):e29597. doi: 10.1002/jmv.29597.


The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in the loss of millions of lives, although a majority of those infected have managed to survive. Consequently, a set of outcomes, identified as long COVID, is now emerging. While the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory system, the impact of COVID-19 extends to various body parts, including the bone. This study aims to investigate the effects of acute SARS-CoV-2 infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains. Monocyte-derived macrophages, which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased postinfection, with no significant impact on cellular viability and redox balance. Both SARS-CoV-2 strains heightened osteoclast formation in a dose-dependent manner, as well as CD51/61 expression and bone resorptive ability. Notably, SARS-CoV-2 induced early pro-inflammatory M1 macrophage polarization, shifting toward an M2-like profile. Osteoclastogenesis-related genes (RANK, NFATc1, DC-STAMP, MMP9) were upregulated, and surprisingly, SARS-CoV-2 variants promoted RANKL-independent osteoclast formation. This thorough investigation illuminates the intricate interplay between SARS-CoV-2 and osteoclast precursors, suggesting potential implications for bone homeostasis and opening new avenues for therapeutic exploration in COVID-19.

Keywords: COVID‐19; RANKL; SARS‐CoV‐2; bone; monocyte‐derived macrophages; osteoclasts.

MeSH terms

  • COVID-19* / metabolism
  • Cell Differentiation
  • Humans
  • Osteoclasts* / metabolism
  • Post-Acute COVID-19 Syndrome
  • SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants