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The abortive SARS-CoV-2 infection of osteoclast precursors promotes their differentiation into osteoclasts
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  • Jorge Quarleri,
  • Franco SVIERCZ,
  • Patricio JARMOLUK,
  • Joshua GODOY COTO,
  • Cintia CEVALLOS,
  • Rosa Nicole FREIBERGER,
  • Cyntia Alicia Marcela LÓPEZ,
  • Irene Lucia ENNIS,
  • M. Victoria Delpino
Jorge Quarleri
Universidad de Buenos Aires

Corresponding Author:[email protected]

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Franco SVIERCZ
Universidad de Buenos Aires
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Patricio JARMOLUK
Universidad de Buenos Aires
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Joshua GODOY COTO
Universidad Nacional de la Plata
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Cintia CEVALLOS
Universidad de Buenos Aires
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Rosa Nicole FREIBERGER
Universidad de Buenos Aires
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Cyntia Alicia Marcela LÓPEZ
Universidad de Buenos Aires
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Irene Lucia ENNIS
Universidad Nacional de la Plata
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M. Victoria Delpino
Universidad de Buenos Aires
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Abstract

The 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 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 (MDM), which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased post-infection, 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 towards 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.
Submitted to Journal of Medical Virology
27 Jan 2024Reviewer(s) Assigned
28 Feb 2024Review(s) Completed, Editorial Evaluation Pending
28 Feb 2024Editorial Decision: Revise Major
31 Mar 2024Review(s) Completed, Editorial Evaluation Pending
01 Apr 2024Editorial Decision: Accept